Clathrin-mediated endocytosis (Homo sapiens)

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2, 5, 7, 11, 16...11, 44, 51, 68, 78...3, 42, 46, 55, 10725, 37, 39, 41, 50...43, 47, 86, 138, 15519, 33, 82, 112, 134...12, 13, 38, 71, 73...53, 11221, 31, 32, 39, 41...15, 23, 59, 83, 84, 100...16, 25, 26, 44, 49...1, 8, 32, 36, 42...45, 82, 93, 104, 1066, 26, 56, 82, 10510, 27, 40, 61, 81...10, 13, 16, 26, 29...4, 14, 18, 19, 22...6, 26, 56, 82, 10530, 34, 43, 47, 84...83, 100, 142, 14935, 43, 47, 86, 130...clathrin-coated endocytic vesiclecytosolPACSIN2 CLTCL1 TAGs p-AVPR2 STON1 UBC(153-228) ARRB1 UBC(77-152) AGFG1 VAMP2 CLTA UBC(609-684) ACTR2 LDLRAP1 SH3GL3 AP2B1 SH3GL2 UBC(153-228) EPN2 GAPVD1 NAd UBC(153-228) SH3GL1 CLTA PACSIN3 HIP1 SNX18 UBB(153-228) ACTR3 PACSIN2 AP-2 dileucine-containing cargo CLTC HSPA8 PICALM AP2S1 UBC(457-532) UBB(153-228) FNBP1L ADR p-DVL2 p-Y371-CBL UBC(229-304) STAM LDLRAP1 ATP GAK p-Y371-CBL DNM3 SH3GL3 ARPC5 UBC(609-684) H2OCLTCL1 REPS1 SH3KBP1 AAK1 AGTR1 CHOL PACSIN1 AGFG1 p-6Y-EGFR FZD4 UBB(153-228) CHRM2 AP2S1 EPS15L1 LDLRAP1 p-Y371-CBL CLTA ITSN2 LRP2 SYNJ1 SNAP91 UBC(77-152) CTTN EPN2 REPS2 ITSN2 ARFGAP1:ARF6:GTPHSPA8 ITSN2 ARPC4 EPS15 SH3KBP1 LDLR DNM2 EGF STAM2 AP2B1 DNM2 HGS SH3GL2 CHOL AP2A2(1-939) HGS DNM2 AP2A2(1-939) REPS1 UBC(609-684) p-6Y-EGFR SH3GL3 N-WASP VAMP7 SYNJ2 BIN1 ITSN1 p-DVL2 PACSIN3 NAd FNBP1L EPN2 UBC(533-608) LDLR VAMP3 TAGs TAGs ARPC1A STON1 FNBP1 LRP2 p-Y850 EPS15 SYNJ1 p-Y850 EPS15 AP2A2(1-939) p-DVL2 AP2S1 PI(4)P:p-T156AP-2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilinEPS15L1 p-T156 AP2M1 AP2B1 SGIP1 ARP2/3 complexVAMP3 HIP1 SNAP91 SH3KBP1 EGF ITSN2 AP2S1 AP2A1 NECAP2 DNM1 SYT8 AP2A1 AAK1 ARPC5 CHOL FNBP1 LRP2 CLTC SNX9 AP2A1 CLTCL1 NECAP2 SNX18 REPS1 FNBP1L STAM FNBP1 DNM1 REPS2 UBC(153-228) EPN1 SYT2 ITSN1 DNM2 EPN1 UBA52(1-76) ATP AP-2 YXXPhi cargo LDLRAP1 AP2A2(1-939) PI(4)P:p-T156AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilinADR UBB(153-228) SNAP91 UBC(229-304) ADR SYT11 UBC(305-380) N4GlycoAsn-PalmS WNT5A(36-380) VAMP8 STON1 SYT8 CTTN AP2A1 ATP ARRB1 TAGs LDLR SH3GL3 UBB(77-152) VAMP8 SH3GL1 AP2B1 AP2A2(1-939) AP2A1 UBC(381-456) UBC(381-456) AP2A1 ITSN2 pS-ADRB2 SYT8 SYT8 PICALM SYT1 cholesterol esters p-Y850 EPS15 TAGs SYT9 p-6Y-EGFR GAK REPS2 DNM:GTPAVP(20-28) SYT11 AGFG1 ARPC3 AP2A2(1-939) STAM2 SH3KBP1 AP2S1 UBB(1-76) UBC(609-684) AP2A2(1-939) STAM p-Y371-CBL PI(4,5)P2:p-T156AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1VAMP7 STAM2 EPS15 EPN1 CHRM2 VAMP3 REPS2 RPS27A(1-76) APOB(28-4563) EPS15 p-Y850 EPS15 HIP1R BIN1 ITSN2 AP2M1 AP2A2(1-939) CTTN PI(4)P:p-T156AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GTP:SYNJsEPN2 SNX9 p-Y850 EPS15 ARPC1A SYT11 CHRM2 EPS15 SNAP91 PACSIN1 AP-2 dileucine-containing cargo AP-2 dileucine-containing cargo CHOL SH3GL1 EPN1 CLTCL1 cholesterol esters UBC(229-304) ARPC4 p-T156 AP2M1 AAK1 UBC(1-76) p-Y371-CBL SYT1 cholesterol esters SGIP1 DNM1 STON2 EPN2 AP2B1 UBB(1-76) EPS15 ARPC3 HGS AP-2 YXXPhi cargo p-Y850 EPS15 PACSIN1 PI4PNAd SYNJ2 p-Y850 EPS15 DNAJC6 DAB2 CHOL EPS15 PL SYT9 CLTA AP2A1 HSPA8:ATPVAMP7 CHOL SH3GL2 AVPR2 N4GlycoAsn-PalmS WNT5A(36-380) PICALM SNAP91 AP2M1 SYT1 SYT9 AP2A2(1-939) cholesterol esters VAMP2 UBB(153-228) SH3GL2 TACR1 EPS15L1 SYNJ1 AP-2 ComplexLDLR EPS15 NECAP2 SYT9 UBA52(1-76) ARPC2 AVP(20-28) DNM3 CLTB GDP SYT8 UBA52(1-76) ITSN1 SH3GL1 AP2S1 SGIP1 p-DVL2 AVP(20-28) UBC(1-76) VAMP7 CLTC HIP1R dimerSYT8 p-T156 AP2M1 NECAP2 CLTB DAB2 AP2B1 TAGs DNM2 NECAP1 HIP1 LRP2 ITSN1 CLTC CLTC ADR DAB2 ITSN1 CLTC p-Y371-CBL N4GlycoAsn-PalmS WNT5A(36-380) AAK1 VAMP8 AP2A1 ARPC1A PACSIN2 VAMP2 VAMP3 SH3KBP1 UBC(153-228) TRIP10 p-T156 AP2M1 SYT8 ATPCHRM2 ARPC1A SNX9 ARPC4 CLTA EPS15L1 ADR OCRL PACSIN3 ARF6 GAK SYNJ1 ARPC3 VAMP8 AP2M1 SYT11 FCHO2 PI(4,5)P2 AP-2 YXXPhi cargo HGS GRB2-1 AVP(20-28) DAB2 UBC(77-152) N-WASP SH3GL1 AVPR2 DNAJC6 N-WASP SYT1 SNAP91 UBC(381-456) CLTC PL SGIP1 DNM1 cholesterol esters SH3GL2 VAMP7 CLTC PL p-T156 AP2M1 EPN1 UBB(77-152) AP2A1 SH3GL3 STAM2 UBC(229-304) ACTR2 EGF SYT11 UBA52(1-76) UBC(77-152) AP2A2(1-939) SNX9 UBC(457-532) DNM3 UBB(77-152) UBB(153-228) VAMP2 SH3GL3 p-Y850 EPS15 AP2M1 AP2M1 UBC(457-532) GTP ARPC5 p-Y850 EPS15 UBC(1-76) AMPH STON1 SYNJ2 PIK3C2ASYT2 FNBP1 SH3GL1 DAB2 RPS27A(1-76) REPS2 p-DVL2 PI4P FCHO2 p-Y371-CBL AP2S1 NECAP2 p-DVL2 RPS27A(1-76) TACR1 LDLR p-DVL2 CLTA SH3GL3 p-T156 AP2M1 UBC(77-152) VAMP3 EPN1 GDP RPS27A(1-76) BIN1 STAM STON1 ADR RPS27A(1-76) ACTR3 p-Y850 EPS15 NAd FZD4 SYNJ2 UBB(1-76) CLTB ARPC1A FNBP1 SNAP91 SYT1 PICALM AP2A2(1-939) EPS15L1 SYT9 AP2M1 SNX9 ARRB2 CHRM2 ARPC1A DAB2 p-Y371-CBL RPS27A(1-76) EPS15 AP2B1 CLTB UBA52(1-76) AP2M1 N-WASP UBC(229-304) PiPICALM AVPR2 GRB2-1 EPS15 UBC(1-76) ARRB2 AP2M1 AGTR1 AP-2 dileucine-containing cargo f-actin UBC(153-228) FZD4 ARRB2 SYNJ2 NECAP2 SGIP1 EPN1 NECAP2 AAK1 LDLR ATP PI(4,5)P2:p-T156AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:PIK3C2AAGTR1 PACSIN1 CLTCL1 STON2 PACSIN1 UBC(381-456) FZD4 UBC(1-76) PI(4,5)P2 PI(4)P:p-T156AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilin:HSPA8:ATPGDP HIP1R CLTA UBB(1-76) AP2A1 UBC(533-608) AP2S1 REPS2 EGF VAMP7 PiAGTR1 GDP HIP1R CLTA BIN1 N4GlycoAsn-PalmS WNT5A(36-380) UBB(1-76) HGS AGFG1 AP2M1 EGF p-Y371-CBL SH3KBP1 p-6Y-EGFR STON1 EPS15 VAMP3 AP2S1 PI(4,5)P2 UBC(305-380) REPS2 p-DVL2 AP2B1 UBB(77-152) APOB(28-4563) NECAP2 UBC(381-456) AP-2 dileucine-containing cargo NAd HIP1 dimerp-DVL2 ARPC2 EPS15L1 SYT8 PICALM NECAP1 ARPC2 PI(4,5)P2:p-T156AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimersARRB1 UBC(381-456) SNX9 pS-ADRB2 VAMP7 HIP1 HGS PICALM N4GlycoAsn-PalmS WNT5A(36-380) AP2A1 EPN1 AP2B1 NECAP1 SYT11 AMPH FZD4 TRIP10 GRB2-1 ITSN1 PI(4,5)P2 APOB(28-4563) SYT2 UBC(609-684) AP-2 YXXPhi cargo GRB2-1 SGIP1 UBC(305-380) AAK1 VAMP2 AGFG1 ADR N4GlycoAsn-PalmS WNT5A(36-380) AMPH SH3GL1 AP2A1 VAMP8 SYT11 ARPC4 ARPC2 REPS2 PI(3,4)P2SH3GL3 TACR1 AP2M1 PICALM ITSN2 CLTCL1 DNM1 PI4P GGC-RAB5C ARFGAP1 HGS REPS2 SGIP1 AP2M1 VAMP2 SH3GL2 BIN1 DNM1 PACSIN3 GGC-RAB5A UBC(229-304) CLTC DNAJC6 UBC(1-76) VAMP3 AP2A1 p-AVPR2 CLTC EGF VAMP2 FZD4 ARPC4 PI(4,5)P2:AP-2:clathrinATPAAK1 ARPC1A STON2 SYT11 PI4P SYNJ2 FNBP1L ACTR3 GRB2-1 CLTA ARPC4 ARPC3 LDLRAP1 UBC(1-76) EPS15 ITSN2 HGS EPS15L1 DNM2 AP-2 dileucine-containing cargo DAB2 HGS p-Y371-CBL LRP2 AVPR2 UBB(1-76) SYT1 NECAP1 OCRL STON2 UBC(77-152) TRIP10 PACSIN3 ARRB1 AP2A2(1-939) FZD4 CLTB SYT8 DNM3 AP2S1 LRP2 N4GlycoAsn-PalmS WNT5A(36-380) AP-2 YXXPhi cargo ITSN2 UBC(457-532) PICALM LRP2 TACR1 UBC(533-608) ARPC1A VAMP7 NAd UBC(457-532) CLTC H2Of-actinAGTR1 ADPEPN1 RPS27A(1-76) ARPC3 ADR SH3GL2 AP2M1 CLTCL1 p-6Y-EGFR AGFG1 ITSN2 STON2 AP-2 dileucine-containing cargo AP2A1 AP2A1 SYT9 ACTR2 ARRB1 HIP1 REPS1 AP2A1 SGIP1 UBC(77-152) PACSIN1 SYNJ2 SYT2 FZD4 CLTB ARPC3 AP2A1 SH3GL1 Cargo recognitionforclathrin-mediatedendocytosisEPS15 OCRL AP2B1 cholesterol esters AP-2 dileucine-containing cargo NECAP1 UBC(153-228) FCHO2 ATP SYT8 AGTR1 ARPC1A p-6Y-EGFR N4GlycoAsn-PalmS WNT5A(36-380) ITSN2 PL UBC(305-380) AP2S1 EPN1 p-Y850 EPS15 AGFG1 UBA52(1-76) AP2S1 AP2B1 GAPVD1 SNAP91 TAGs SYT1 TRIP10 EPN1 REPS1 SNX18 GGC-RAB5B UBC(457-532) LDLRAP1 CLTCL1 f-actin CLASP proteins:cargop-6Y-EGFR CLTA p-6Y-EGFR AP2M1 UBC(609-684) PL AP2S1 SYT11 UBC(1-76) AGTR1 EPN2 FCHO1 p-6Y-EGFR pS-ADRB2 UBC(1-76) EGF STAM2 ARPC4 p-T156 AP2M1 CLTA CLTCL1 TACR1 VAMP8 AP2A2(1-939) NAd FNBP1 FNBP1L AP-2 YXXPhi cargo ACTR2 SNX18 EPS15 AGTR1 VAMP3 SYT8 AAK1 AGTR1 FNBP1 AP2A2(1-939) ITSN1 ACTR3 CHRM2 SH3GL1 FCHO1 CLTC UBC(305-380) UBB(77-152) EGF HGS pS-ADRB2 PACSIN1 UBB(153-228) ARPC4 AGFG1 DNM:GDPUBC(457-532) AP2B1 VAMP3 AP2B1 p-AVPR2 SH3GL3 CLTCL1 FCHO1 ITSNsEPN1 AP-2 YXXPhi cargo NECAP2 SYT8 PL STAM2 cholesterol esters TACR1 AP2A1 f-actin SYNJ1 ADP VAMP7 AP2M1 UBC(609-684) SH3GL1 RPS27A(1-76) REPS1 STAM f-actin PACSIN1 UBC(381-456) AMPH CHOL AP-2 dileucine-containing cargo CLTB UBB(1-76) UBC(305-380) UBC(229-304) UBC(609-684) SGIP1 UBC(533-608) EPS15 DNM2 CLTA SGIP1 SYT2 NECAP1 AGTR1 ARPC3 LDLRAP1 UBB(1-76) UBB(153-228) EPN2 N4GlycoAsn-PalmS WNT5A(36-380) EPN2 HIP1R pS-ADRB2 AP-2 dileucine-containing cargo REPS2 SYT9 CLTB UBC(305-380) UBC(153-228) STAM AP2M1 AMPH ATP ITSN1 UBC(229-304) UBA52(1-76) SYT9 HIP1R ARPC5 SH3GL3 VAMP3 SGIP1 AP2M1 LDLR UBB(77-152) ITSN2 SYT8 EGF AP-2 dileucine-containing cargo f-actin p-AVPR2 CLTB CLTA UBC(381-456) EPN2 PIP5K1Cp-DVL2 UBA52(1-76) AMPH ARRB2 UBC(229-304) UBC(609-684) DNAJC6 GGC-RAB5C GDP ACTR2 AP2B1 PI4P SYT2 BIN1 STAM ARRB1 REPS1 PICALM LDLR ARRB1 EPN2 CHOL HGS CLTA PACSIN2 REPS2 SYT2 FCHO2 TRIP10 REPS2 AP2S1 APOB(28-4563) UBC(1-76) CLTA AAK1 p-DVL2 ARRB2 UBC(381-456) VAMP8 UBC(381-456) p-6Y-EGFR VAMP2 REPS1 DNM3 UBB(153-228) GAPVD1 DNAJC6 NECAP1 p-Y371-CBL NECAP2 DNM1 OCRL UBC(533-608) UBB(153-228) ARPC3 AP2S1 CHOL UBC(305-380) SH3GL3 UBB(77-152) FNBP1L AP2B1 SNX9 AP2S1 APOB(28-4563) PL EPN2 PI(4,5)P2 UBC(77-152) STON1 AP2M1 UBB(153-228) FCHO1,2 dimerLDLRAP1 BIN1 p-DVL2 PACSIN3 AAK1SYT1 p-Y371-CBL UBB(1-76) CHOL TAGs GRB2-1 UBC(229-304) GTP CLTA AP2A2(1-939) N4GlycoAsn-PalmS WNT5A(36-380) AP2S1 EPS15L1 SNX9 UBC(381-456) OCRL CTTN p-DVL2 STAM SH3KBP1 STON1 UBC(77-152) pS-ADRB2 PI(4,5)P2:p-T156AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteinsVAMP2 STAM p-DVL2 UBC(77-152) GAK EPS15L1 SGIP1 SH3GL1 NECAP2 UBC(457-532) REPS2 CLTB UBC(609-684) UBA52(1-76) SNX18 ARPC2 NAd p-6Y-EGFR UBC(1-76) PACSIN2 UBC(381-456) VAMP8 DNM2 STON1 GGC-RAB5B ARRB2 SYT8 CLTA NECAP1 GRB2-1 ADR EPS15L1 SYNJs,OCRLPACSIN1 AGTR1 RPS27A(1-76) AP2A1 CLTB REPS2 p-Y371-CBL UBC(533-608) CLTC DNAJC6 TACR1 VAMP2 APOB(28-4563) PACSIN dimersSYT11 UBC(305-380) ITSN2 STON1 cholesterol esters ATPp-Y371-CBL DNM3 PiSTAM2 SNAP91 HGS LRP2 SYT1 NECAPsAP2A2(1-939) UBC(1-76) SNX18 AP2A2(1-939) ATP ITSN2 ARRB2 SNX18 GDP ITSN1 UBC(229-304) UBB(77-152) SGIP1 ARPC5 AP2M1 STON2 AP2M1 AMPH p-Y371-CBL AP2A1 PI4P HIP1 SYT2 ARPC3 AP2A2(1-939) SYT9 UBB(77-152) DNM3 TACR1 TAGs NAd UBC(533-608) CLTC SH3KBP1 STAM2 TRIP10 f-actin SYT9 CLTA SNAP91 SH3GL2 PACSIN3 GGC-RAB5A LRP2 CLTA GTP EPN2 STON1 CTTN ITSN1 UBB(153-228) NECAP1 NAd AGFG1 PL AP2S1 STON2 PACSIN1 UBB(1-76) VAMP3 ITSN1 SNAP91 STAM CLTA UBC(533-608) UBC(229-304) CLTC PI(4,5)P2SH3GL2 UBC(381-456) TACR1 NECAP2 N-WASP SH3KBP1 SNX9 FZD4 SGIP1 AVP(20-28) UBC(381-456) UBB(153-228) DNM2 CLTC PACSIN2 PI(4,5)P2 p-T156 AP2M1 SYT1 UBC(533-608) SGIP1 UBC(77-152) UBC(153-228) UBC(229-304) N-WASP UBC(229-304) OCRL UBA52(1-76) SH3GL3 TACR1 STAM STON1 AP2A1 ARPC5 GAPVD1 BIN1 RPS27A(1-76) SH3GL3 UBC(153-228) SYT1 AMPH UBC(381-456) EPN1 ARRB2 LDLRAP1 PIK3C2A REPS1 AVP(20-28) FNBP1 p-T156 AP2M1 cholesterol esters REPS1 DNM3 EPN2 UBC(305-380) BIN1 UBC(533-608) HIP1 SNX9 NAd DAB2 APOB(28-4563) VAMP2 CLTA VAMP3 CLTA cholesterol esters CTTN AGFG1 CHRM2 DAB2 p-T156 AP2M1 OCRL HIP1R UBB(1-76) LDLR UBC(457-532) UBC(609-684) ACTR3 ACTR3 PICALM UBB(77-152) VAMP8 PICALM AVP(20-28) AP2A1 AMPH AP-2 YXXPhi cargo p-Y850 EPS15 PI(4,5)P2 p-Y850 EPS15 HGS N-WASP EPN1 VAMP7 cholesterol esters REPS1 CLTC SH3GL2 UBB(1-76) PI(4,5)P2 ACTR3 clathrin triskelionHIP1 CHOL EPN1 AMPH UBA52(1-76) VAMP8 NECAP1 CLTB CHRM2 TACR1 PACSIN2 TRIP10 AP2M1 CLTC CHRM2 CLTCL1 SYNJ1 FZD4 PACSIN2 ARRB1 p-Y371-CBL AP2A2(1-939) PL EPN2 p-Y371-CBL p-Y371-CBL pS-ADRB2 SNX18 VAMP7 AP2B1 UBC(609-684) f-actin SGIP1 EPN1 FNBP1L SYT11 p-AVPR2 AAK1 AP2B1 CLTCL1 PL REPS1 BIN1 PICALM N-WASP EGF HGS AP-2 dileucine-containing cargo GTP UBB(1-76) AP2S1 p-T156 AP2M1 ACTR2 GGC-RAB5:GDP:GAPVD1CTTN UBB(77-152) SH3KBP1 SNAP91 ACTR2 PI(4)P:p-T156AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJsUBC(153-228) REPS1 AAK1 FCHO1 REPS1 STON2 AP2A2(1-939) HGS ARRB2 SYT2 AP2M1 CLTB LDLR DNM3 AMPH pS-ADRB2 CLTC SYT11 APOB(28-4563) PI(4,5)P2 AGTR1 UBC(77-152) AP2A1 PACSIN2 GRB2-1 NECAP2 FNBP1 ARRB2 GDP FZD4 AVP(20-28) LRP2 SYT2 SNX18 PICALM N-WASP GAK UBB(153-228) GGC-RAB5C EPN1 GRB2-1 GTP SH3GL1 ARRB2 cholesterol esters AGFG1 SH3GL1 LDLR N4GlycoAsn-PalmS WNT5A(36-380) STON2 UBA52(1-76) SH3GL2 UBC(533-608) SYT2 CLTA SYT9 UBC(533-608) FNBP1 dimerARRB1 AP2M1 TRIP10 dimerSTAM2 CHRM2 PL REPS1 SH3GLsPI(4)P:p-T156AP-2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilinAMPH LDLR NECAP1 p-6Y-EGFR AP2A2(1-939) ARRB1 FNBP1L ARPC2 PACSIN3 SYT9 p-6Y-EGFR AP2M1 PI(4,5)P2:AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1AGTR1 FNBP1 STAM2 NECAP1 ACTR2 SYT11 AP2A1 FCHO2 ARRB2 ACTR2 UBC(1-76) LRP2 DAB2 PACSIN3 GTP SYT8 CLTC FZD4 UBC(533-608) CLTA UBB(77-152) AVP(20-28) UBC(77-152) STAM2 ARPC5 p-AVPR2 ARRB1 NECAP2 CLTC EPN1 STON1 AAK1 TAGs CLTCL1 CLTB AGFG1 UBC(457-532) LRP2 SYNJ1 STAM2 DAB2 SH3GL3 SYT2 VAMP8 EGF SNAP91 UBC(457-532) RPS27A(1-76) STON2 VAMP8 DNM2 PACSIN1 LRP2 NAd FNBP1 PI4P SYNJ1 CLTB ITSN1 AVPR2 PI4P CLTC EPS15 GDP VAMP8 SH3GL2 ARRB1 SH3KBP1 SGIP1ARRB1 AP-2 YXXPhi cargo AP2A1 SYT2 EPS15 TACR1 AP2A1 CHOL SNAP91 STON2 SH3KBP1 EPN1 GRB2-1 UBC(305-380) N4GlycoAsn-PalmS WNT5A(36-380) p-AVPR2 CLTCL1 ITSN1 SNX9 STAM2 SYT9 AVP(20-28) EPN1 REPS1EPS15L1 RPS27A(1-76) VAMP3 CTTN FCHO2 AGTR1 ACTR2 DAB2 SYT9 N4GlycoAsn-PalmS WNT5A(36-380) VAMP2 TACR1 EGF DAB2 clathrin triskelionCLTC DNM3 REPS1 AP2B1 p-6Y-EGFR p-Y371-CBL cholesterol esters AP2A2(1-939) ITSN1 RPS27A(1-76) SNAP91 UBC(533-608) FZD4 UBC(1-76) LDLR N-WASP AP-2 YXXPhi cargo UBC(153-228) UBC(77-152) ARPC2 SYT2 SYT9 ATP VAMP3 PACSIN2 REPS2 SH3GL3 PL EPS15L1 AP2B1 DAB2 WASL,CTTNAP-2 dileucine-containing cargo VAMP7 ATP AP2S1 OCRL FNBP1L UBC(305-380) PACSIN3 UBC(457-532) LDLRAP1 PACSIN2 AP2A2(1-939) BIN1 PACSIN2 FZD4 GRB2-1 cholesterol esters GTP ITSN2 p-T156 AP2M1 AP2S1 TACR1 CLTC pS-ADRB2 p-DVL2 SYNJ2 EPS15 NECAP1 AAK1 UBC(77-152) AP2A1 ARRB1 PI4PDNM1 AP2S1 SH3GL1 CHOL AAK1 TAGs STAM AP2M1 CLTB ARPC5 AAK1CLTCL1 DNM1 AP2B1 UBC(229-304) AGFG1 AP2B1 ARPC5 SNX18 AVPR2 AP-2 ComplexFNBP1L UBC(609-684) NECAP1 ARPC1A pS-ADRB2 BIN1 STON2 AP2B1 PI(4,5)P2:p-T156AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargoDNM2 ARPC3 p-Y371-CBL LDLRAP1 UBC(533-608) N4GlycoAsn-PalmS WNT5A(36-380) TRIP10 EPS15L1 CHRM2 APOB(28-4563) UBC(609-684) GGC-RAB5B HIP1R UBA52(1-76) ACTR2 PI(4,5)P2:p-T156AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GTP:SYNJsPACSIN3 GRB2-1 VAMP7 SNX9 CTTN FNBP1 ADR AP2A2(1-939) EPS15 f-actin UBC(1-76) AP2S1 STAM ACTR3 HIP1R APOB(28-4563) GGC-RAB5A pS-ADRB2 ITSN1 p-Y371-CBL ARPC3 ARPC2 EPS15L1 ITSN2 LDLR CLTA UBB(1-76) PL NECAP1 CLTC SYT11 STON2 TRIP10 SH3KBP1 AGFG1 AMPH:BIN1CLTCL1 EPN1 GGC-RAB5A ACTR3 NAd UBC(457-532) PI(4)P:p-T156AP-2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilinGGC-RAB5:GTP:GAPVD1AP2A2(1-939) EGF DNM1 HIP1R CLASP proteins:cargoTACR1 HIP1 SH3GL2 ARPC4 HSPA8 ITSN1 UBB(153-228) FNBP1L dimerAP2B1 HIP1R UBB(77-152) AVPR2 SYT11 TRIP10 PACSIN3 PICALM UBC(153-228) ACTR3 ARRB2 SH3GL1 TAGs SYT1 EPN1 APOB(28-4563) AP2M1 GRB2-1 f-actin GAK,DNAJC6AP-2 YXXPhi cargo FZD4 f-actin ADPp-T156 AP2M1 CLTA VAMP7 p-6Y-EGFR DAB2 HIP1 p-Y371-CBL AP2B1 FNBP1L UBB(77-152) UBB(77-152) AP2S1 ATP SNX18 UBC(305-380) PL OCRL EPS15VAMP2 FCHO1 AP2S1 ARRB2 CLTA AP-2 YXXPhi cargo ADR EPS15L1 ARPC4 AP2S1 SNX9,18ATP UBA52(1-76) STON1 EPN2 ADR AP2M1 SH3KBP1 NECAP1 SYT1 UBB(1-76) GGC-RAB5B CHOL pS-ADRB2 AP2B1 TAGs STON2 HIP1R CTTN VAMP2 CLTC TRIP10 AP-2 YXXPhi cargo NECAP2 NECAP2 NAd AP2S1 CLTC cholesterol esters SYNJ1 RPS27A(1-76) CLTB AP2A1 clathrin:HSPA8:ADPLRP2 TRIP10 pS-ADRB2 SYT2 SH3KBP1 AP2M1 ARPC4 ARRB1 LDLRAP1 SYNJ2 AP2B1 APOB(28-4563) ADR EGF FCHO1 AP2B1 STAM2 TAGs GRB2-1 p-AVPR2 ADPARPC2 FNBP1L STAM2 VAMP7 LDLRAP1 p-Y850 EPS15 LRP2 SYT1 CLTA CHRM2 ARPC2 LDLRAP1 VAMP2 ARRB2 GGC-RAB5:GTP:GAPVD1ADR AVP(20-28) AP2B1 AP2A2(1-939) PACSIN1 AP2S1 PI(4,5)P2 AVP(20-28) SH3GL1 AP-2 YXXPhi cargo STON1 AP2A2(1-939) LDLRAP1 UBA52(1-76) ITSN2 VAMP8 STAM CTTN AP2A1 UBC(153-228) AP2A2(1-939) AP2A2(1-939) ACTR3 p-Y850 EPS15 UBC(609-684) UBC(305-380) PL ADR DNM3 STON2 SH3GL3 H2OCLTA APOB(28-4563) pS-ADRB2 SH3GL2 STAM DNM1 CHOL GRB2-1 APOB(28-4563) SNX18 LDLR AP2B1 AP-2 dileucine-containing cargo VAMP3 AVP(20-28) ATP ARPC5 EPN1 PI4PNAd EGF AVP(20-28) ITSN1 ARPC5 UBC(153-228) CHRM2 SH3GL2 ARPC1A AP2M1 TAGs UBC(457-532) UBC(305-380) HIP1 ARPC2 GAK GGC-RAB5C SYT1 AP-2 YXXPhi cargo CLTC N-WASP p-Y371-CBL UBC(457-532) N4GlycoAsn-PalmS WNT5A(36-380) PI(4,5)P2:AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1AVP(20-28) APOB(28-4563) PI(4,5)P2:p-T156AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GTPAGTR1 RPS27A(1-76) pS-ADRB2 CLTCL1 AP2S1 VAMP8 SH3GL2 CLTC CHRM2 CHRM2 AP-2 dileucine-containing cargo AGFG1 9, 64, 88, 91, 113...17, 48, 60, 77, 1519, 64, 88, 91, 113...9, 64, 88, 91, 113...9, 64, 88, 91, 113...9, 64, 88, 91, 113...9, 64, 88, 91, 113...17, 48, 60, 77, 1519, 64, 88, 91, 113...17, 48, 60, 77, 15117, 48, 60, 77, 15111, 50, 57, 62, 87...9, 64, 88, 91, 113...17, 48, 60, 77, 15117, 48, 60, 77, 1519, 64, 88, 91, 113...50, 6617, 48, 60, 77, 1519, 64, 88, 91, 113...17, 48, 60, 77, 1519, 64, 88, 91, 113...17, 48, 60, 77, 1519, 64, 88, 91, 113...17, 48, 60, 77, 15117, 48, 60, 77, 1519, 64, 88, 91, 113...17, 48, 60, 77, 1519, 64, 88, 91, 113...17, 48, 60, 77, 15117, 48, 60, 77, 1519, 64, 88, 91, 113...17, 48, 60, 77, 151


Description

Clathrin-mediated endocytosis (CME) is one of a number of process that control the uptake of material from the plasma membrane, and leads to the formation of clathrin-coated vesicles (Pearse et al, 1975; reviewed in Robinson, 2015; McMahon and Boucrot, 2011; Kirchhausen et al, 2014). CME contributes to signal transduction by regulating the cell surface expression and signaling of receptor tyrosine kinases (RTKs) and G-protein coupled receptors (GPCRs). Most RTKs exhibit a robust increase in internalization rate after binding specific ligands; however, some RTKs may also exhibit significant ligand-independent internalization (reviewed in Goh and Sorkin, 2013). CME controls RTK and GPCR signaling by organizing signaling both within the plasma membrane and on endosomes (reviewed in Eichel et al, 2016; Garay et al, 2015; Vieira et al, 1996; Sorkin and von Zastrow, 2014; Di Fiori and von Zastrow, 2014; Barbieri et al, 2016). CME also contributes to the uptake of material such as metabolites, hormones and other proteins from the extracellular space, and regulates membrane composition by recycling membrane components and/or targeting them for degradation.


Clathrin-mediated endocytosis involves initiation of clathrin-coated pit (CCP) formation, cargo selection, coat assembly and stabilization, membrane scission and vesicle uncoating. Although for simplicity in this pathway, the steps leading to a mature CCP are represented in a linear and temporally distinct fashion, the formation of a clathrin-coated vesicle is a highly heterogeneous process and clear temporal boundaries between these processes may not exist (see for instance Taylor et al, 2011; Antonescu et al, 2011; reviewed in Kirchhausen et al, 2014). Cargo selection in particular is a critical aspect of the formation of a mature and stable CCP, and many of the proteins involved in the initiation and maturation of a CCP contribute to cargo selection and are themselves stabilized upon incorporation of cargo into the nascent vesicle (reviewed in Kirchhausen et al, 2014; McMahon and Boucrot, 2011).



Although the clathrin triskelion was identified early as a major component of the coated vesicles, clathrin does not bind directly to membranes or to the endocytosed cargo. Vesicle formation instead relies on many proteins and adaptors that can bind the plasma membrane and interact with cargo molecules. Cargo selection depends on the recognition of endocytic signals in cytoplasmic tails of the cargo proteins by adaptors that interact with components of the vesicle's inner coat. The classic adaptor for clathrin-coated vesicles is the tetrameric AP-2 complex, which along with clathrin was identified early as a major component of the coat. Some cargo indeed bind directly to AP-2, but subsequent work has revealed a large family of proteins collectively known as CLASPs (clathrin- associated sorting proteins) that mediate the recruitment of diverse cargo into the emerging clathrin-coated vesicles (reviewed in Traub and Bonifacino, 2013). Many of these CLASP proteins themselves interact with AP-2 and clathrin, coordinating cargo recruitment with coat formation (Schmid et al, 2006; Edeling et al, 2006; reviewed in Traub and Bonifacino, 2013; Kirchhausen et al, 2014).


Initiation of CCP formation is also influenced by lipid composition, regulated by clathrin-associated phosphatases and kinases (reviewed in Picas et al, 2016). The plasma membrane is enriched in PI(4,5)P2. Many of the proteins involved in initiating clathrin-coated pit formation bind to PI(4,5)P2 and induce membrane curvature through their BAR domains (reviewed in McMahon and Boucrot, 2011; Daumke et al, 2014). Epsin also contributes to early membrane curvature through its Epsin N-terminal homology (ENTH) domain, which promotes membrane curvature by inserting into the lipid bilayer (Ford et al, 2002).

Following initiation, some CCPs progress to formation of vesicles, while others undergo disassembly at the cell surface without producing vesicles (Ehrlich et al, 2004; Loerke et al, 2009; Loerke et al, 2011; Aguet et al, 2013; Taylor et al, 2011). The assembly and stabilization of nascent CCPs is regulated by several proteins and lipids (Mettlen et al, 2009; Antonescu et al, 2011).


Maturation of the emerging clathrin-coated vesicle is accompanied by further changes in the lipid composition of the membrane and increased membrane curvature, promoted by the recruitment of N-BAR domain containing proteins (reviewed in Daumke et al, 2014; Ferguson and De Camilli, 2012; Picas et al, 2016). Some N-BAR domain containing proteins also contribute to the recruitment of the large GTPase dynamin, which is responsible for scission of the mature vesicle from the plasma membrane (Koh et al, 2007; Lundmark and Carlsson, 2003; Soulet et al, 2005; David et al, 1996; Owen et al, 1998; Shupliakov et al, 1997; Taylor et al, 2011; Ferguson et al, 2009; Aguet et al, 2013; Posor et al, 2013; Chappie et al, 2010; Shnyrova et al, 2013; reviewed in Mettlen et al, 2009; Daumke et al, 2014). After vesicle scission, the clathrin coat is dissociated from the new vesicle by the ATPase HSPA8 (also known as HSC70) and its DNAJ cofactor auxilin, priming the vesicle for fusion with a subsequent endocytic compartment and releasing clathrin for reuse (reviewed in McMahon and Boucrot, 2011; Sousa and Laufer, 2015). View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 8856828
Reactome-version 
Reactome version: 62
Reactome Author 
Reactome Author: Rothfels, Karen

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Bibliography

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  1. Shupliakov O, Löw P, Grabs D, Gad H, Chen H, David C, Takei K, De Camilli P, Brodin L.; ''Synaptic vesicle endocytosis impaired by disruption of dynamin-SH3 domain interactions.''; PubMed Europe PMC Scholia
  2. Brett TJ, Traub LM, Fremont DH.; ''Accessory protein recruitment motifs in clathrin-mediated endocytosis.''; PubMed Europe PMC Scholia
  3. Saffarian S, Cocucci E, Kirchhausen T.; ''Distinct dynamics of endocytic clathrin-coated pits and coated plaques.''; PubMed Europe PMC Scholia
  4. Rawet M, Levi-Tal S, Szafer-Glusman E, Parnis A, Cassel D.; ''ArfGAP1 interacts with coat proteins through tryptophan-based motifs.''; PubMed Europe PMC Scholia
  5. Collawn JF, Stangel M, Kuhn LA, Esekogwu V, Jing SQ, Trowbridge IS, Tainer JA.; ''Transferrin receptor internalization sequence YXRF implicates a tight turn as the structural recognition motif for endocytosis.''; PubMed Europe PMC Scholia
  6. Gallop JL, McMahon HT.; ''BAR domains and membrane curvature: bringing your curves to the BAR.''; PubMed Europe PMC Scholia
  7. Yarar D, Waterman-Storer CM, Schmid SL.; ''SNX9 couples actin assembly to phosphoinositide signals and is required for membrane remodeling during endocytosis.''; PubMed Europe PMC Scholia
  8. Chang-Ileto B, Frere SG, Chan RB, Voronov SV, Roux A, Di Paolo G.; ''Synaptojanin 1-mediated PI(4,5)P2 hydrolysis is modulated by membrane curvature and facilitates membrane fission.''; PubMed Europe PMC Scholia
  9. Lundmark R, Carlsson SR.; ''Sorting nexin 9 participates in clathrin-mediated endocytosis through interactions with the core components.''; PubMed Europe PMC Scholia
  10. Sousa R, Lafer EM.; ''The role of molecular chaperones in clathrin mediated vesicular trafficking.''; PubMed Europe PMC Scholia
  11. Chappie JS, Acharya S, Leonard M, Schmid SL, Dyda F.; ''G domain dimerization controls dynamin's assembly-stimulated GTPase activity.''; PubMed Europe PMC Scholia
  12. Fotin A, Cheng Y, Grigorieff N, Walz T, Harrison SC, Kirchhausen T.; ''Structure of an auxilin-bound clathrin coat and its implications for the mechanism of uncoating.''; PubMed Europe PMC Scholia
  13. Beck KA, Keen JH.; ''Interaction of phosphoinositide cycle intermediates with the plasma membrane-associated clathrin assembly protein AP-2.''; PubMed Europe PMC Scholia
  14. Milosevic I, Giovedi S, Lou X, Raimondi A, Collesi C, Shen H, Paradise S, O'Toole E, Ferguson S, Cremona O, De Camilli P.; ''Recruitment of endophilin to clathrin-coated pit necks is required for efficient vesicle uncoating after fission.''; PubMed Europe PMC Scholia
  15. Itoh T, Erdmann KS, Roux A, Habermann B, Werner H, De Camilli P.; ''Dynamin and the actin cytoskeleton cooperatively regulate plasma membrane invagination by BAR and F-BAR proteins.''; PubMed Europe PMC Scholia
  16. Mani M, Lee SY, Lucast L, Cremona O, Di Paolo G, De Camilli P, Ryan TA.; ''The dual phosphatase activity of synaptojanin1 is required for both efficient synaptic vesicle endocytosis and reavailability at nerve terminals.''; PubMed Europe PMC Scholia
  17. McLauchlan H, Newell J, Morrice N, Osborne A, West M, Smythe E.; ''A novel role for Rab5-GDI in ligand sequestration into clathrin-coated pits.''; PubMed Europe PMC Scholia
  18. Stimpson HE, Toret CP, Cheng AT, Pauly BS, Drubin DG.; ''Early-arriving Syp1p and Ede1p function in endocytic site placement and formation in budding yeast.''; PubMed Europe PMC Scholia
  19. Liu AP, Aguet F, Danuser G, Schmid SL.; ''Local clustering of transferrin receptors promotes clathrin-coated pit initiation.''; PubMed Europe PMC Scholia
  20. Edeling MA, Mishra SK, Keyel PA, Steinhauser AL, Collins BM, Roth R, Heuser JE, Owen DJ, Traub LM.; ''Molecular switches involving the AP-2 beta2 appendage regulate endocytic cargo selection and clathrin coat assembly.''; PubMed Europe PMC Scholia
  21. Modregger J, Ritter B, Witter B, Paulsson M, Plomann M.; ''All three PACSIN isoforms bind to endocytic proteins and inhibit endocytosis.''; PubMed Europe PMC Scholia
  22. David C, McPherson PS, Mundigl O, de Camilli P.; ''A role of amphiphysin in synaptic vesicle endocytosis suggested by its binding to dynamin in nerve terminals.''; PubMed Europe PMC Scholia
  23. Jackson AP, Flett A, Smythe C, Hufton L, Wettey FR, Smythe E.; ''Clathrin promotes incorporation of cargo into coated pits by activation of the AP2 adaptor micro2 kinase.''; PubMed Europe PMC Scholia
  24. Conner SD, Schröter T, Schmid SL.; ''AAK1-mediated micro2 phosphorylation is stimulated by assembled clathrin.''; PubMed Europe PMC Scholia
  25. Shin N, Lee S, Ahn N, Kim SA, Ahn SG, YongPark Z, Chang S.; ''Sorting nexin 9 interacts with dynamin 1 and N-WASP and coordinates synaptic vesicle endocytosis.''; PubMed Europe PMC Scholia
  26. Johannessen LE, Pedersen NM, Pedersen KW, Madshus IH, Stang E.; ''Activation of the epidermal growth factor (EGF) receptor induces formation of EGF receptor- and Grb2-containing clathrin-coated pits.''; PubMed Europe PMC Scholia
  27. Letourneur F, Klausner RD.; ''A novel di-leucine motif and a tyrosine-based motif independently mediate lysosomal targeting and endocytosis of CD3 chains.''; PubMed Europe PMC Scholia
  28. Schmidt U, Briese S, Leicht K, Schürmann A, Joost HG, Al-Hasani H.; ''Endocytosis of the glucose transporter GLUT8 is mediated by interaction of a dileucine motif with the beta2-adaptin subunit of the AP-2 adaptor complex.''; PubMed Europe PMC Scholia
  29. Owen DJ, Wigge P, Vallis Y, Moore JD, Evans PR, McMahon HT.; ''Crystal structure of the amphiphysin-2 SH3 domain and its role in the prevention of dynamin ring formation.''; PubMed Europe PMC Scholia
  30. Levecque C, Velayos-Baeza A, Holloway ZG, Monaco AP.; ''The dyslexia-associated protein KIAA0319 interacts with adaptor protein 2 and follows the classical clathrin-mediated endocytosis pathway.''; PubMed Europe PMC Scholia
  31. Huang F, Khvorova A, Marshall W, Sorkin A.; ''Analysis of clathrin-mediated endocytosis of epidermal growth factor receptor by RNA interference.''; PubMed Europe PMC Scholia
  32. Henne WM, Boucrot E, Meinecke M, Evergren E, Vallis Y, Mittal R, McMahon HT.; ''FCHo proteins are nucleators of clathrin-mediated endocytosis.''; PubMed Europe PMC Scholia
  33. Barouch W, Prasad K, Greene L, Eisenberg E.; ''Auxilin-induced interaction of the molecular chaperone Hsc70 with clathrin baskets.''; PubMed Europe PMC Scholia
  34. Faller EM, Ghazawi FM, Cavar M, MacPherson PA.; ''IL-7 induces clathrin-mediated endocytosis of CD127 and subsequent degradation by the proteasome in primary human CD8 T cells.''; PubMed Europe PMC Scholia
  35. Ford MG, Jenni S, Nunnari J.; ''The crystal structure of dynamin.''; PubMed Europe PMC Scholia
  36. Boulant S, Kural C, Zeeh JC, Ubelmann F, Kirchhausen T.; ''Actin dynamics counteract membrane tension during clathrin-mediated endocytosis.''; PubMed Europe PMC Scholia
  37. Bai M, Gad H, Turacchio G, Cocucci E, Yang JS, Li J, Beznoussenko GV, Nie Z, Luo R, Fu L, Collawn JF, Kirchhausen T, Luini A, Hsu VW.; ''ARFGAP1 promotes AP-2-dependent endocytosis.''; PubMed Europe PMC Scholia
  38. Chavrier P, Parton RG, Hauri HP, Simons K, Zerial M.; ''Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments.''; PubMed Europe PMC Scholia
  39. Metzler M, Legendre-Guillemin V, Gan L, Chopra V, Kwok A, McPherson PS, Hayden MR.; ''HIP1 functions in clathrin-mediated endocytosis through binding to clathrin and adaptor protein 2.''; PubMed Europe PMC Scholia
  40. Ritter B, Denisov AY, Philie J, Allaire PD, Legendre-Guillemin V, Zylbergold P, Gehring K, McPherson PS.; ''The NECAP PHear domain increases clathrin accessory protein binding potential.''; PubMed Europe PMC Scholia
  41. Picas L, Gaits-Iacovoni F, Goud B.; ''The emerging role of phosphoinositide clustering in intracellular trafficking and signal transduction.''; PubMed Europe PMC Scholia
  42. Ritter B, Murphy S, Dokainish H, Girard M, Gudheti MV, Kozlov G, Halin M, Philie J, Jorgensen EM, Gehring K, McPherson PS.; ''NECAP 1 regulates AP-2 interactions to control vesicle size, number, and cargo during clathrin-mediated endocytosis.''; PubMed Europe PMC Scholia
  43. Wandinger-Ness A, Zerial M.; ''Rab proteins and the compartmentalization of the endosomal system.''; PubMed Europe PMC Scholia
  44. Lemmon SK.; ''Clathrin uncoating: Auxilin comes to life.''; PubMed Europe PMC Scholia
  45. Faelber K, Posor Y, Gao S, Held M, Roske Y, Schulze D, Haucke V, Noé F, Daumke O.; ''Crystal structure of nucleotide-free dynamin.''; PubMed Europe PMC Scholia
  46. Eichel K, Jullié D, von Zastrow M.; ''β-Arrestin drives MAP kinase signalling from clathrin-coated structures after GPCR dissociation.''; PubMed Europe PMC Scholia
  47. Greener T, Zhao X, Nojima H, Eisenberg E, Greene LE.; ''Role of cyclin G-associated kinase in uncoating clathrin-coated vesicles from non-neuronal cells.''; PubMed Europe PMC Scholia
  48. Shin N, Ahn N, Chang-Ileto B, Park J, Takei K, Ahn SG, Kim SA, Di Paolo G, Chang S.; ''SNX9 regulates tubular invagination of the plasma membrane through interaction with actin cytoskeleton and dynamin 2.''; PubMed Europe PMC Scholia
  49. Guan R, Dai H, Harrison SC, Kirchhausen T.; ''Structure of the PTEN-like region of auxilin, a detector of clathrin-coated vesicle budding.''; PubMed Europe PMC Scholia
  50. Robinson MS.; ''Forty Years of Clathrin-coated Vesicles.''; PubMed Europe PMC Scholia
  51. Böcking T, Aguet F, Harrison SC, Kirchhausen T.; ''Single-molecule analysis of a molecular disassemblase reveals the mechanism of Hsc70-driven clathrin uncoating.''; PubMed Europe PMC Scholia
  52. Verstreken P, Koh TW, Schulze KL, Zhai RG, Hiesinger PR, Zhou Y, Mehta SQ, Cao Y, Roos J, Bellen HJ.; ''Synaptojanin is recruited by endophilin to promote synaptic vesicle uncoating.''; PubMed Europe PMC Scholia
  53. Kelly BT, McCoy AJ, Späte K, Miller SE, Evans PR, Höning S, Owen DJ.; ''A structural explanation for the binding of endocytic dileucine motifs by the AP2 complex.''; PubMed Europe PMC Scholia
  54. Hunker CM, Galvis A, Kruk I, Giambini H, Veisaga ML, Barbieri MA.; ''Rab5-activating protein 6, a novel endosomal protein with a role in endocytosis.''; PubMed Europe PMC Scholia
  55. Dergai O, Novokhatska O, Dergai M, Skrypkina I, Tsyba L, Moreau J, Rynditch A.; ''Intersectin 1 forms complexes with SGIP1 and Reps1 in clathrin-coated pits.''; PubMed Europe PMC Scholia
  56. Schuske KR, Richmond JE, Matthies DS, Davis WS, Runz S, Rube DA, van der Bliek AM, Jorgensen EM.; ''Endophilin is required for synaptic vesicle endocytosis by localizing synaptojanin.''; PubMed Europe PMC Scholia
  57. Hollopeter G, Lange JJ, Zhang Y, Vu TN, Gu M, Ailion M, Lambie EJ, Slaughter BD, Unruh JR, Florens L, Jorgensen EM.; ''The membrane-associated proteins FCHo and SGIP are allosteric activators of the AP2 clathrin adaptor complex.''; PubMed Europe PMC Scholia
  58. Scheele U, Kalthoff C, Ungewickell E.; ''Multiple interactions of auxilin 1 with clathrin and the AP-2 adaptor complex.''; PubMed Europe PMC Scholia
  59. Ricotta D, Conner SD, Schmid SL, von Figura K, Honing S.; ''Phosphorylation of the AP2 mu subunit by AAK1 mediates high affinity binding to membrane protein sorting signals.''; PubMed Europe PMC Scholia
  60. Höning S, Ricotta D, Krauss M, Späte K, Spolaore B, Motley A, Robinson M, Robinson C, Haucke V, Owen DJ.; ''Phosphatidylinositol-(4,5)-bisphosphate regulates sorting signal recognition by the clathrin-associated adaptor complex AP2.''; PubMed Europe PMC Scholia
  61. Rapoport I, Boll W, Yu A, Böcking T, Kirchhausen T.; ''A motif in the clathrin heavy chain required for the Hsc70/auxilin uncoating reaction.''; PubMed Europe PMC Scholia
  62. Boucrot E, Saffarian S, Zhang R, Kirchhausen T.; ''Roles of AP-2 in clathrin-mediated endocytosis.''; PubMed Europe PMC Scholia
  63. Nández R, Balkin DM, Messa M, Liang L, Paradise S, Czapla H, Hein MY, Duncan JS, Mann M, De Camilli P.; ''A role of OCRL in clathrin-coated pit dynamics and uncoating revealed by studies of Lowe syndrome cells.''; PubMed Europe PMC Scholia
  64. Rothnie A, Clarke AR, Kuzmic P, Cameron A, Smith CJ.; ''A sequential mechanism for clathrin cage disassembly by 70-kDa heat-shock cognate protein (Hsc70) and auxilin.''; PubMed Europe PMC Scholia
  65. Nunez D, Antonescu C, Mettlen M, Liu A, Schmid SL, Loerke D, Danuser G.; ''Hotspots organize clathrin-mediated endocytosis by efficient recruitment and retention of nucleating resources.''; PubMed Europe PMC Scholia
  66. Palacios F, Schweitzer JK, Boshans RL, D'Souza-Schorey C.; ''ARF6-GTP recruits Nm23-H1 to facilitate dynamin-mediated endocytosis during adherens junctions disassembly.''; PubMed Europe PMC Scholia
  67. Ritter B, Philie J, Girard M, Tung EC, Blondeau F, McPherson PS.; ''Identification of a family of endocytic proteins that define a new alpha-adaptin ear-binding motif.''; PubMed Europe PMC Scholia
  68. Schlossman DM, Schmid SL, Braell WA, Rothman JE.; ''An enzyme that removes clathrin coats: purification of an uncoating ATPase.''; PubMed Europe PMC Scholia
  69. Thieman JR, Mishra SK, Ling K, Doray B, Anderson RA, Traub LM.; ''Clathrin regulates the association of PIPKIgamma661 with the AP-2 adaptor beta2 appendage.''; PubMed Europe PMC Scholia
  70. Stenmark H.; ''Rab GTPases as coordinators of vesicle traffic.''; PubMed Europe PMC Scholia
  71. Soohoo AL, Puthenveedu MA.; ''Divergent modes for cargo-mediated control of clathrin-coated pit dynamics.''; PubMed Europe PMC Scholia
  72. Jadot M, Canfield WM, Gregory W, Kornfeld S.; ''Characterization of the signal for rapid internalization of the bovine mannose 6-phosphate/insulin-like growth factor-II receptor.''; PubMed Europe PMC Scholia
  73. Henne WM, Kent HM, Ford MG, Hegde BG, Daumke O, Butler PJ, Mittal R, Langen R, Evans PR, McMahon HT.; ''Structure and analysis of FCHo2 F-BAR domain: a dimerizing and membrane recruitment module that effects membrane curvature.''; PubMed Europe PMC Scholia
  74. Mao Y, Balkin DM, Zoncu R, Erdmann KS, Tomasini L, Hu F, Jin MM, Hodsdon ME, De Camilli P.; ''A PH domain within OCRL bridges clathrin-mediated membrane trafficking to phosphoinositide metabolism.''; PubMed Europe PMC Scholia
  75. Gaidarov I, Zhao Y, Keen JH.; ''Individual phosphoinositide 3-kinase C2alpha domain activities independently regulate clathrin function.''; PubMed Europe PMC Scholia
  76. Wilbur JD, Chen CY, Manalo V, Hwang PK, Fletterick RJ, Brodsky FM.; ''Actin binding by Hip1 (huntingtin-interacting protein 1) and Hip1R (Hip1-related protein) is regulated by clathrin light chain.''; PubMed Europe PMC Scholia
  77. Billcliff PG, Lowe M.; ''Inositol lipid phosphatases in membrane trafficking and human disease.''; PubMed Europe PMC Scholia
  78. Sato M, Sato K, Fonarev P, Huang CJ, Liou W, Grant BD.; ''Caenorhabditis elegans RME-6 is a novel regulator of RAB-5 at the clathrin-coated pit.''; PubMed Europe PMC Scholia
  79. Schmid EM, Ford MG, Burtey A, Praefcke GJ, Peak-Chew SY, Mills IG, Benmerah A, McMahon HT.; ''Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly.''; PubMed Europe PMC Scholia
  80. Keyel PA, Mishra SK, Roth R, Heuser JE, Watkins SC, Traub LM.; ''A single common portal for clathrin-mediated endocytosis of distinct cargo governed by cargo-selective adaptors.''; PubMed Europe PMC Scholia
  81. Garay C, Judge G, Lucarelli S, Bautista S, Pandey R, Singh T, Antonescu CN.; ''Epidermal growth factor-stimulated Akt phosphorylation requires clathrin or ErbB2 but not receptor endocytosis.''; PubMed Europe PMC Scholia
  82. Lundmark R, Carlsson SR.; ''SNX9 - a prelude to vesicle release.''; PubMed Europe PMC Scholia
  83. Taylor MJ, Perrais D, Merrifield CJ.; ''A high precision survey of the molecular dynamics of mammalian clathrin-mediated endocytosis.''; PubMed Europe PMC Scholia
  84. Motley A, Bright NA, Seaman MN, Robinson MS.; ''Clathrin-mediated endocytosis in AP-2-depleted cells.''; PubMed Europe PMC Scholia
  85. Mettlen M, Stoeber M, Loerke D, Antonescu CN, Danuser G, Schmid SL.; ''Endocytic accessory proteins are functionally distinguished by their differential effects on the maturation of clathrin-coated pits.''; PubMed Europe PMC Scholia
  86. Cocucci E, Aguet F, Boulant S, Kirchhausen T.; ''The first five seconds in the life of a clathrin-coated pit.''; PubMed Europe PMC Scholia
  87. Gaidarov I, Smith ME, Domin J, Keen JH.; ''The class II phosphoinositide 3-kinase C2alpha is activated by clathrin and regulates clathrin-mediated membrane trafficking.''; PubMed Europe PMC Scholia
  88. Ford MG, Mills IG, Peter BJ, Vallis Y, Praefcke GJ, Evans PR, McMahon HT.; ''Curvature of clathrin-coated pits driven by epsin.''; PubMed Europe PMC Scholia
  89. Ehrlich M, Boll W, Van Oijen A, Hariharan R, Chandran K, Nibert ML, Kirchhausen T.; ''Endocytosis by random initiation and stabilization of clathrin-coated pits.''; PubMed Europe PMC Scholia
  90. Loerke D, Mettlen M, Schmid SL, Danuser G.; ''Measuring the hierarchy of molecular events during clathrin-mediated endocytosis.''; PubMed Europe PMC Scholia
  91. Xing Y, Böcking T, Wolf M, Grigorieff N, Kirchhausen T, Harrison SC.; ''Structure of clathrin coat with bound Hsc70 and auxilin: mechanism of Hsc70-facilitated disassembly.''; PubMed Europe PMC Scholia
  92. Waelter S, Scherzinger E, Hasenbank R, Nordhoff E, Lurz R, Goehler H, Gauss C, Sathasivam K, Bates GP, Lehrach H, Wanker EE.; ''The huntingtin interacting protein HIP1 is a clathrin and alpha-adaptin-binding protein involved in receptor-mediated endocytosis.''; PubMed Europe PMC Scholia
  93. Krauss M, Kinuta M, Wenk MR, De Camilli P, Takei K, Haucke V.; ''ARF6 stimulates clathrin/AP-2 recruitment to synaptic membranes by activating phosphatidylinositol phosphate kinase type Igamma.''; PubMed Europe PMC Scholia
  94. Cremona O, Di Paolo G, Wenk MR, Lüthi A, Kim WT, Takei K, Daniell L, Nemoto Y, Shears SB, Flavell RA, McCormick DA, De Camilli P.; ''Essential role of phosphoinositide metabolism in synaptic vesicle recycling.''; PubMed Europe PMC Scholia
  95. Moravec R, Conger KK, D'Souza R, Allison AB, Casanova JE.; ''BRAG2/GEP100/IQSec1 interacts with clathrin and regulates α5β1 integrin endocytosis through activation of ADP ribosylation factor 5 (Arf5).''; PubMed Europe PMC Scholia
  96. Di Paolo G, De Camilli P.; ''Phosphoinositides in cell regulation and membrane dynamics.''; PubMed Europe PMC Scholia
  97. Umasankar PK, Sanker S, Thieman JR, Chakraborty S, Wendland B, Tsang M, Tsang M, Traub LM.; ''Distinct and separable activities of the endocytic clathrin-coat components Fcho1/2 and AP-2 in developmental patterning.''; PubMed Europe PMC Scholia
  98. Haffner C, Takei K, Chen H, Ringstad N, Hudson A, Butler MH, Salcini AE, Di Fiore PP, De Camilli P.; ''Synaptojanin 1: localization on coated endocytic intermediates in nerve terminals and interaction of its 170 kDa isoform with Eps15.''; PubMed Europe PMC Scholia
  99. Semerdjieva S, Shortt B, Maxwell E, Singh S, Fonarev P, Hansen J, Schiavo G, Grant BD, Smythe E.; ''Coordinated regulation of AP2 uncoating from clathrin-coated vesicles by rab5 and hRME-6.''; PubMed Europe PMC Scholia
  100. Soulet F, Yarar D, Leonard M, Schmid SL.; ''SNX9 regulates dynamin assembly and is required for efficient clathrin-mediated endocytosis.''; PubMed Europe PMC Scholia
  101. Reider A, Barker SL, Mishra SK, Im YJ, Maldonado-Báez L, Hurley JH, Traub LM, Wendland B.; ''Syp1 is a conserved endocytic adaptor that contains domains involved in cargo selection and membrane tubulation.''; PubMed Europe PMC Scholia
  102. Wasiak S, Legendre-Guillemin V, Puertollano R, Blondeau F, Girard M, de Heuvel E, Boismenu D, Bell AW, Bonifacino JS, McPherson PS.; ''Enthoprotin: a novel clathrin-associated protein identified through subcellular proteomics.''; PubMed Europe PMC Scholia
  103. Yoshida Y, Kinuta M, Abe T, Liang S, Araki K, Cremona O, Di Paolo G, Moriyama Y, Yasuda T, De Camilli P, Takei K.; ''The stimulatory action of amphiphysin on dynamin function is dependent on lipid bilayer curvature.''; PubMed Europe PMC Scholia
  104. Fotin A, Cheng Y, Sliz P, Grigorieff N, Harrison SC, Kirchhausen T, Walz T.; ''Molecular model for a complete clathrin lattice from electron cryomicroscopy.''; PubMed Europe PMC Scholia
  105. Legendre-Guillemin V, Metzler M, Charbonneau M, Gan L, Chopra V, Philie J, Hayden MR, McPherson PS.; ''HIP1 and HIP12 display differential binding to F-actin, AP2, and clathrin. Identification of a novel interaction with clathrin light chain.''; PubMed Europe PMC Scholia
  106. Aguet F, Antonescu CN, Mettlen M, Schmid SL, Danuser G.; ''Advances in analysis of low signal-to-noise images link dynamin and AP2 to the functions of an endocytic checkpoint.''; PubMed Europe PMC Scholia
  107. Goh LK, Sorkin A.; ''Endocytosis of receptor tyrosine kinases.''; PubMed Europe PMC Scholia
  108. Posor Y, Eichhorn-Gruenig M, Puchkov D, Schöneberg J, Ullrich A, Lampe A, Müller R, Zarbakhsh S, Gulluni F, Hirsch E, Krauss M, Schultz C, Schmoranzer J, Noé F, Haucke V.; ''Spatiotemporal control of endocytosis by phosphatidylinositol-3,4-bisphosphate.''; PubMed Europe PMC Scholia
  109. Mishra SK, Agostinelli NR, Brett TJ, Mizukami I, Ross TS, Traub LM.; ''Clathrin- and AP-2-binding sites in HIP1 uncover a general assembly role for endocytic accessory proteins.''; PubMed Europe PMC Scholia
  110. Doray B, Lee I, Knisely J, Bu G, Kornfeld S.; ''The gamma/sigma1 and alpha/sigma2 hemicomplexes of clathrin adaptors AP-1 and AP-2 harbor the dileucine recognition site.''; PubMed Europe PMC Scholia
  111. Sorkin A, von Zastrow M.; ''Endocytosis and signalling: intertwining molecular networks.''; PubMed Europe PMC Scholia
  112. Shin HW, Hayashi M, Christoforidis S, Lacas-Gervais S, Hoepfner S, Wenk MR, Modregger J, Uttenweiler-Joseph S, Wilm M, Nystuen A, Frankel WN, Solimena M, De Camilli P, Zerial M.; ''An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway.''; PubMed Europe PMC Scholia
  113. Henderson DM, Conner SD.; ''A novel AAK1 splice variant functions at multiple steps of the endocytic pathway.''; PubMed Europe PMC Scholia
  114. Mettlen M, Loerke D, Yarar D, Danuser G, Schmid SL.; ''Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis.''; PubMed Europe PMC Scholia
  115. Massol RH, Boll W, Griffin AM, Kirchhausen T.; ''A burst of auxilin recruitment determines the onset of clathrin-coated vesicle uncoating.''; PubMed Europe PMC Scholia
  116. Daumke O, Roux A, Haucke V.; ''BAR domain scaffolds in dynamin-mediated membrane fission.''; PubMed Europe PMC Scholia
  117. Paleotti O, Macia E, Luton F, Klein S, Partisani M, Chardin P, Kirchhausen T, Franco M.; ''The small G-protein Arf6GTP recruits the AP-2 adaptor complex to membranes.''; PubMed Europe PMC Scholia
  118. Barbieri E, Di Fiore PP, Sigismund S.; ''Endocytic control of signaling at the plasma membrane.''; PubMed Europe PMC Scholia
  119. Loerke D, Mettlen M, Yarar D, Jaqaman K, Jaqaman H, Danuser G, Schmid SL.; ''Cargo and dynamin regulate clathrin-coated pit maturation.''; PubMed Europe PMC Scholia
  120. McMahon HT, Boucrot E.; ''Molecular mechanism and physiological functions of clathrin-mediated endocytosis.''; PubMed Europe PMC Scholia
  121. Gaidarov I, Santini F, Warren RA, Keen JH.; ''Spatial control of coated-pit dynamics in living cells.''; PubMed Europe PMC Scholia
  122. Perera RM, Zoncu R, Lucast L, De Camilli P, Toomre D.; ''Two synaptojanin 1 isoforms are recruited to clathrin-coated pits at different stages.''; PubMed Europe PMC Scholia
  123. Meinecke M, Boucrot E, Camdere G, Hon WC, Mittal R, McMahon HT.; ''Cooperative recruitment of dynamin and BIN/amphiphysin/Rvs (BAR) domain-containing proteins leads to GTP-dependent membrane scission.''; PubMed Europe PMC Scholia
  124. Chappie JS, Mears JA, Fang S, Leonard M, Schmid SL, Milligan RA, Hinshaw JE, Dyda F.; ''A pseudoatomic model of the dynamin polymer identifies a hydrolysis-dependent powerstroke.''; PubMed Europe PMC Scholia
  125. Di Fiore PP, von Zastrow M.; ''Endocytosis, signaling, and beyond.''; PubMed Europe PMC Scholia
  126. Koh TW, Korolchuk VI, Wairkar YP, Jiao W, Evergren E, Pan H, Zhou Y, Venken KJ, Shupliakov O, Robinson IM, O'Kane CJ, Bellen HJ.; ''Eps15 and Dap160 control synaptic vesicle membrane retrieval and synapse development.''; PubMed Europe PMC Scholia
  127. Christoforidis S, Miaczynska M, Ashman K, Wilm M, Zhao L, Yip SC, Waterfield MD, Backer JM, Zerial M.; ''Phosphatidylinositol-3-OH kinases are Rab5 effectors.''; PubMed Europe PMC Scholia
  128. Kirchhausen T, Owen D, Harrison SC.; ''Molecular structure, function, and dynamics of clathrin-mediated membrane traffic.''; PubMed Europe PMC Scholia
  129. Neumann S, Schmid SL.; ''Dual role of BAR domain-containing proteins in regulating vesicle release catalyzed by the GTPase, dynamin-2.''; PubMed Europe PMC Scholia
  130. Taylor MJ, Lampe M, Merrifield CJ.; ''A feedback loop between dynamin and actin recruitment during clathrin-mediated endocytosis.''; PubMed Europe PMC Scholia
  131. Ferguson SM, Raimondi A, Paradise S, Shen H, Mesaki K, Ferguson A, Destaing O, Ko G, Takasaki J, Cremona O, O' Toole E, De Camilli P.; ''Coordinated actions of actin and BAR proteins upstream of dynamin at endocytic clathrin-coated pits.''; PubMed Europe PMC Scholia
  132. Sweitzer SM, Hinshaw JE.; ''Dynamin undergoes a GTP-dependent conformational change causing vesiculation.''; PubMed Europe PMC Scholia
  133. Takei K, Slepnev VI, Haucke V, De Camilli P.; ''Functional partnership between amphiphysin and dynamin in clathrin-mediated endocytosis.''; PubMed Europe PMC Scholia
  134. Ferguson SM, De Camilli P.; ''Dynamin, a membrane-remodelling GTPase.''; PubMed Europe PMC Scholia
  135. Bairstow SF, Ling K, Su X, Firestone AJ, Carbonara C, Anderson RA.; ''Type Igamma661 phosphatidylinositol phosphate kinase directly interacts with AP2 and regulates endocytosis.''; PubMed Europe PMC Scholia
  136. Vieira AV, Lamaze C, Schmid SL.; ''Control of EGF receptor signaling by clathrin-mediated endocytosis.''; PubMed Europe PMC Scholia
  137. Traub LM, Bonifacino JS.; ''Cargo recognition in clathrin-mediated endocytosis.''; PubMed Europe PMC Scholia
  138. Dittman J, Ryan TA.; ''Molecular circuitry of endocytosis at nerve terminals.''; PubMed Europe PMC Scholia
  139. Ungewickell E, Ungewickell H, Holstein SE, Lindner R, Prasad K, Barouch W, Martin B, Greene LE, Eisenberg E.; ''Role of auxilin in uncoating clathrin-coated vesicles.''; PubMed Europe PMC Scholia
  140. Mettlen M, Pucadyil T, Ramachandran R, Schmid SL.; ''Dissecting dynamin's role in clathrin-mediated endocytosis.''; PubMed Europe PMC Scholia
  141. Marie B, Sweeney ST, Poskanzer KE, Roos J, Kelly RB, Davis GW.; ''Dap160/intersectin scaffolds the periactive zone to achieve high-fidelity endocytosis and normal synaptic growth.''; PubMed Europe PMC Scholia
  142. Puthenveedu MA, von Zastrow M.; ''Cargo regulates clathrin-coated pit dynamics.''; PubMed Europe PMC Scholia
  143. Antonescu CN, Aguet F, Danuser G, Schmid SL.; ''Phosphatidylinositol-(4,5)-bisphosphate regulates clathrin-coated pit initiation, stabilization, and size.''; PubMed Europe PMC Scholia
  144. Storch S, Braulke T.; ''Multiple C-terminal motifs of the 46-kDa mannose 6-phosphate receptor tail contribute to efficient binding of medium chains of AP-2 and AP-3.''; PubMed Europe PMC Scholia
  145. Traub LM.; ''Tickets to ride: selecting cargo for clathrin-regulated internalization.''; PubMed Europe PMC Scholia
  146. Ogata S, Fukuda M.; ''Lysosomal targeting of Limp II membrane glycoprotein requires a novel Leu-Ile motif at a particular position in its cytoplasmic tail.''; PubMed Europe PMC Scholia
  147. Erdmann KS, Mao Y, McCrea HJ, Zoncu R, Lee S, Paradise S, Modregger J, Biemesderfer D, Toomre D, De Camilli P.; ''A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway.''; PubMed Europe PMC Scholia
  148. Conner SD, Schmid SL.; ''Identification of an adaptor-associated kinase, AAK1, as a regulator of clathrin-mediated endocytosis.''; PubMed Europe PMC Scholia
  149. Domin J, Gaidarov I, Smith ME, Keen JH, Waterfield MD.; ''The class II phosphoinositide 3-kinase PI3K-C2alpha is concentrated in the trans-Golgi network and present in clathrin-coated vesicles.''; PubMed Europe PMC Scholia
  150. Kim MH, Hersh LB.; ''The vesicular acetylcholine transporter interacts with clathrin-associated adaptor complexes AP-1 and AP-2.''; PubMed Europe PMC Scholia
  151. Kamioka Y, Fukuhara S, Sawa H, Nagashima K, Masuda M, Matsuda M, Mochizuki N.; ''A novel dynamin-associating molecule, formin-binding protein 17, induces tubular membrane invaginations and participates in endocytosis.''; PubMed Europe PMC Scholia
  152. Pearse BM.; ''Coated vesicles from pig brain: purification and biochemical characterization.''; PubMed Europe PMC Scholia
  153. Owen DJ, Evans PR.; ''A structural explanation for the recognition of tyrosine-based endocytotic signals.''; PubMed Europe PMC Scholia
  154. Hinshaw JE, Schmid SL.; ''Dynamin self-assembles into rings suggesting a mechanism for coated vesicle budding.''; PubMed Europe PMC Scholia
  155. Olusanya O, Andrews PD, Swedlow JR, Smythe E.; ''Phosphorylation of threonine 156 of the mu2 subunit of the AP2 complex is essential for endocytosis in vitro and in vivo.''; PubMed Europe PMC Scholia
  156. Gu M, Liu Q, Watanabe S, Sun L, Hollopeter G, Grant BD, Jorgensen EM.; ''AP2 hemicomplexes contribute independently to synaptic vesicle endocytosis.''; PubMed Europe PMC Scholia
  157. Krauss M, Kukhtina V, Pechstein A, Haucke V.; ''Stimulation of phosphatidylinositol kinase type I-mediated phosphatidylinositol (4,5)-bisphosphate synthesis by AP-2mu-cargo complexes.''; PubMed Europe PMC Scholia
  158. Shimada A, Niwa H, Tsujita K, Suetsugu S, Nitta K, Hanawa-Suetsugu K, Akasaka R, Nishino Y, Toyama M, Chen L, Liu ZJ, Wang BC, Yamamoto M, Terada T, Miyazawa A, Tanaka A, Sugano S, Shirouzu M, Nagayama K, Takenawa T, Yokoyama S.; ''Curved EFC/F-BAR-domain dimers are joined end to end into a filament for membrane invagination in endocytosis.''; PubMed Europe PMC Scholia
  159. Cestra G, Castagnoli L, Dente L, Minenkova O, Petrelli A, Migone N, Hoffmüller U, Schneider-Mergener J, Cesareni G.; ''The SH3 domains of endophilin and amphiphysin bind to the proline-rich region of synaptojanin 1 at distinct sites that display an unconventional binding specificity.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
115077view17:02, 25 January 2021ReactomeTeamReactome version 75
113559view13:13, 2 November 2020DeSlOntology Term : 'regulatory pathway' added !
113558view13:12, 2 November 2020DeSlOntology Term : 'clathrin-mediated endocytosis pathway' added !
113519view11:59, 2 November 2020ReactomeTeamReactome version 74
112718view16:12, 9 October 2020ReactomeTeamReactome version 73
101634view11:49, 1 November 2018ReactomeTeamreactome version 66
101170view21:36, 31 October 2018ReactomeTeamreactome version 65
100696view20:09, 31 October 2018ReactomeTeamreactome version 64
100246view16:54, 31 October 2018ReactomeTeamreactome version 63
99798view15:19, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99348view12:48, 31 October 2018ReactomeTeamreactome version 62
93371view11:21, 9 August 2017ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AAK1 ProteinQ2M2I8 (Uniprot-TrEMBL)
AAK1ProteinQ2M2I8 (Uniprot-TrEMBL)
ACTR2 ProteinP61160 (Uniprot-TrEMBL)
ACTR3 ProteinP61158 (Uniprot-TrEMBL)
ADP MetaboliteCHEBI:16761 (ChEBI)
ADPMetaboliteCHEBI:16761 (ChEBI)
ADR MetaboliteCHEBI:28918 (ChEBI)
AGFG1 ProteinP52594 (Uniprot-TrEMBL)
AGTR1 ProteinP30556 (Uniprot-TrEMBL)
AMPH ProteinP49418 (Uniprot-TrEMBL)
AMPH:BIN1ComplexR-HSA-8868606 (Reactome)
AP-2 ComplexComplexR-HSA-167712 (Reactome)
AP-2 YXXPhi cargo R-HSA-8866232 (Reactome)
AP-2 YXXPhi cargo R-HSA-8869159 (Reactome)
AP-2 dileucine-containing cargo R-HSA-8866234 (Reactome)
AP-2 dileucine-containing cargo R-HSA-8869156 (Reactome)
AP2A1 ProteinO95782 (Uniprot-TrEMBL)
AP2A2(1-939) ProteinO94973 (Uniprot-TrEMBL)
AP2B1 ProteinP63010 (Uniprot-TrEMBL)
AP2M1 ProteinQ96CW1 (Uniprot-TrEMBL)
AP2S1 ProteinP53680 (Uniprot-TrEMBL)
APOB(28-4563) ProteinP04114 (Uniprot-TrEMBL)
ARF6 ProteinP62330 (Uniprot-TrEMBL)
ARFGAP1 ProteinQ8N6T3 (Uniprot-TrEMBL)
ARFGAP1:ARF6:GTPComplexR-HSA-8871133 (Reactome)
ARP2/3 complexComplexR-HSA-8868713 (Reactome)
ARPC1A ProteinQ92747 (Uniprot-TrEMBL)
ARPC2 ProteinO15144 (Uniprot-TrEMBL)
ARPC3 ProteinO15145 (Uniprot-TrEMBL)
ARPC4 ProteinP59998 (Uniprot-TrEMBL)
ARPC5 ProteinO15511 (Uniprot-TrEMBL)
ARRB1 ProteinP49407 (Uniprot-TrEMBL)
ARRB2 ProteinP32121 (Uniprot-TrEMBL)
ATP MetaboliteCHEBI:15422 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
AVP(20-28) ProteinP01185 (Uniprot-TrEMBL)
AVPR2 ProteinP30518 (Uniprot-TrEMBL)
BIN1 ProteinO00499 (Uniprot-TrEMBL)
CHOL MetaboliteCHEBI:16113 (ChEBI)
CHRM2 ProteinP08172 (Uniprot-TrEMBL)
CLASP proteins:cargoComplexR-HSA-8867603 (Reactome)
CLASP proteins:cargoComplexR-HSA-8868710 (Reactome)
CLTA ProteinP09496 (Uniprot-TrEMBL)
CLTB ProteinP09497 (Uniprot-TrEMBL)
CLTC ProteinQ00610 (Uniprot-TrEMBL)
CLTCL1 ProteinP53675 (Uniprot-TrEMBL)
CTTN ProteinQ14247 (Uniprot-TrEMBL)
Cargo recognition

for clathrin-mediated

endocytosis
PathwayR-HSA-8856825 (Reactome) Recruitment of plasma membrane-localized cargo into clathrin-coated endocytic vesicles is mediated by interaction with a variety of clathrin-interacting proteins collectively called CLASPs (clathrin-associated sorting proteins). CLASP proteins, which may be monomeric or tetrameric, are recruited to the plasma membrane through interaction with phosphoinsitides and recognize linear or conformational sequences or post-translational modifications in the cytoplasmic tails of the cargo protein. Through bivalent interactions with clathrin and/or other CLASP proteins, they bridge the recruitment of the cargo to the emerging clathrin coated pit (reviewed in Traub and Bonifacino, 2013). The tetrameric AP-2 complex, first identified in early studies of clathrin-mediated endocytosis, was at one time thought to be the primary CLASP protein involved in cargo recognition at the plasma membrane, and indeed plays a key role in the endocytosis of cargo carrying dileucine- or tyrosine-based motifs.

A number of studies have been performed to test whether AP-2 is essential for all forms of clathrin-mediated endocytosis (Keyel et al, 2006; Motely et al, 2003; Huang et al, 2004; Boucrot et al, 2010; Henne et al, 2010; Johannessen et al, 2006; Gu et al, 2013; reviewed in Traub, 2009; McMahon and Boucrot, 2011). Although depletion of AP-2 differentially affects the endocytosis of different cargo, extensive depletion of AP-2 through RNAi reduces clathrin-coated pit formation by 80-90%, and the CCPs that do form still contain AP-2, highlighting the critcical role of this complex in CME (Johannessen et al, 2006; Boucrot et al, 2010; Henne et al, 2010).


In addition to AP-2, a wide range of other CLASPs including proteins of the beta-arrestin, stonin and epsin families, engage sorting motifs in other cargo and interact either with clathrin, AP-2 or each other to facilitate assembly of a clathin-coated pit (reviewed in Traub and Bonifacino, 2013).
DAB2 ProteinP98082 (Uniprot-TrEMBL)
DNAJC6 ProteinO75061 (Uniprot-TrEMBL)
DNM1 ProteinQ05193 (Uniprot-TrEMBL)
DNM2 ProteinP50570 (Uniprot-TrEMBL)
DNM3 ProteinQ9UQ16 (Uniprot-TrEMBL)
DNM:GDPComplexR-HSA-8868609 (Reactome)
DNM:GTPComplexR-HSA-8868235 (Reactome)
EGF ProteinP01133 (Uniprot-TrEMBL)
EPN1 ProteinQ9Y6I3 (Uniprot-TrEMBL)
EPN2 ProteinO95208 (Uniprot-TrEMBL)
EPS15 ProteinP42566 (Uniprot-TrEMBL)
EPS15L1 ProteinQ9UBC2 (Uniprot-TrEMBL)
EPS15ProteinP42566 (Uniprot-TrEMBL)
FCHO1 ProteinO14526 (Uniprot-TrEMBL)
FCHO1,2 dimerComplexR-HSA-8862270 (Reactome)
FCHO2 ProteinQ0JRZ9 (Uniprot-TrEMBL)
FNBP1 ProteinQ96RU3 (Uniprot-TrEMBL)
FNBP1 dimerComplexR-HSA-8868046 (Reactome)
FNBP1L ProteinQ5T0N5 (Uniprot-TrEMBL)
FNBP1L dimerComplexR-HSA-8868045 (Reactome)
FZD4 ProteinQ9ULV1 (Uniprot-TrEMBL)
GAK ProteinO14976 (Uniprot-TrEMBL)
GAK,DNAJC6ComplexR-HSA-8868618 (Reactome)
GAPVD1 ProteinQ14C86 (Uniprot-TrEMBL)
GDP MetaboliteCHEBI:17552 (ChEBI)
GGC-RAB5:GDP:GAPVD1ComplexR-HSA-8871139 (Reactome)
GGC-RAB5:GTP:GAPVD1ComplexR-HSA-8871142 (Reactome)
GGC-RAB5A ProteinP20339 (Uniprot-TrEMBL)
GGC-RAB5B ProteinP61020 (Uniprot-TrEMBL)
GGC-RAB5C ProteinP51148 (Uniprot-TrEMBL)
GRB2-1 ProteinP62993-1 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
HGS ProteinO14964 (Uniprot-TrEMBL)
HIP1 ProteinO00291 (Uniprot-TrEMBL)
HIP1 dimerComplexR-HSA-8868219 (Reactome)
HIP1R ProteinO75146 (Uniprot-TrEMBL)
HIP1R dimerComplexR-HSA-8868221 (Reactome)
HSPA8 ProteinP11142 (Uniprot-TrEMBL)
HSPA8:ATPComplexR-HSA-5251937 (Reactome)
ITSN1 ProteinQ15811 (Uniprot-TrEMBL)
ITSN2 ProteinQ9NZM3 (Uniprot-TrEMBL)
ITSNsComplexR-HSA-8862274 (Reactome)
LDLR ProteinP01130 (Uniprot-TrEMBL)
LDLRAP1 ProteinQ5SW96 (Uniprot-TrEMBL)
LRP2 ProteinP98164 (Uniprot-TrEMBL)
N-WASP ProteinO00401 (Uniprot-TrEMBL)
N4GlycoAsn-PalmS WNT5A(36-380) ProteinP41221 (Uniprot-TrEMBL)
NAd MetaboliteCHEBI:18357 (ChEBI)
NECAP1 ProteinQ8NC96 (Uniprot-TrEMBL)
NECAP2 ProteinQ9NVZ3 (Uniprot-TrEMBL)
NECAPsComplexR-HSA-8863469 (Reactome)
OCRL ProteinQ01968 (Uniprot-TrEMBL)
PACSIN dimersComplexR-HSA-8868621 (Reactome)
PACSIN1 ProteinQ9BY11 (Uniprot-TrEMBL)
PACSIN2 ProteinQ9UNF0 (Uniprot-TrEMBL)
PACSIN3 ProteinQ9UKS6 (Uniprot-TrEMBL)
PI(3,4)P2MetaboliteCHEBI:16152 (ChEBI)
PI(4)P:p-T156 AP-2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilinComplexR-HSA-8868620 (Reactome)
PI(4)P:p-T156 AP-2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilinComplexR-HSA-8871149 (Reactome)
PI(4)P:p-T156 AP-2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilinGGC-RAB5:GTP:GAPVD1ComplexR-HSA-8871150 (Reactome)
PI(4)P:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilin:HSPA8:ATPComplexR-HSA-8868627 (Reactome)
PI(4)P:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilinComplexR-HSA-8868626 (Reactome)
PI(4)P:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJsComplexR-HSA-8868624 (Reactome)
PI(4)P:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GTP:SYNJsComplexR-HSA-8868629 (Reactome)
PI(4,5)P2 MetaboliteCHEBI:18348 (ChEBI)
PI(4,5)P2:AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1ComplexR-HSA-8868048 (Reactome)
PI(4,5)P2:AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1ComplexR-HSA-8862276 (Reactome)
PI(4,5)P2:AP-2:clathrinComplexR-HSA-8871153 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:PIK3C2AComplexR-HSA-8868051 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargoComplexR-HSA-8867753 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1ComplexR-HSA-8856806 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GTP:SYNJsComplexR-HSA-8868634 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GTPComplexR-HSA-8868234 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimersComplexR-HSA-8868232 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteinsComplexR-HSA-8867751 (Reactome)
PI(4,5)P2MetaboliteCHEBI:18348 (ChEBI)
PI4P MetaboliteCHEBI:17526 (ChEBI)
PI4PMetaboliteCHEBI:17526 (ChEBI)
PICALM ProteinQ13492 (Uniprot-TrEMBL)
PIK3C2A ProteinO00443 (Uniprot-TrEMBL)
PIK3C2AProteinO00443 (Uniprot-TrEMBL)
PIP5K1CProteinO60331 (Uniprot-TrEMBL)
PL MetaboliteCHEBI:16247 (ChEBI)
PiMetaboliteCHEBI:18367 (ChEBI)
REPS1 ProteinQ96D71 (Uniprot-TrEMBL)
REPS1ProteinQ96D71 (Uniprot-TrEMBL)
REPS2 ProteinQ8NFH8 (Uniprot-TrEMBL)
RPS27A(1-76) ProteinP62979 (Uniprot-TrEMBL)
SGIP1 ProteinQ9BQI5 (Uniprot-TrEMBL)
SGIP1ProteinQ9BQI5 (Uniprot-TrEMBL)
SH3GL1 ProteinQ99961 (Uniprot-TrEMBL)
SH3GL2 ProteinQ99962 (Uniprot-TrEMBL)
SH3GL3 ProteinQ99963 (Uniprot-TrEMBL)
SH3GLsComplexR-HSA-8867746 (Reactome)
SH3KBP1 ProteinQ96B97 (Uniprot-TrEMBL)
SNAP91 ProteinO60641 (Uniprot-TrEMBL)
SNX18 ProteinQ96RF0 (Uniprot-TrEMBL)
SNX9 ProteinQ9Y5X1 (Uniprot-TrEMBL)
SNX9,18ComplexR-HSA-8868040 (Reactome)
STAM ProteinQ92783 (Uniprot-TrEMBL)
STAM2 ProteinO75886 (Uniprot-TrEMBL)
STON1 ProteinQ9Y6Q2 (Uniprot-TrEMBL)
STON2 ProteinQ8WXE9 (Uniprot-TrEMBL)
SYNJ1 ProteinO43426 (Uniprot-TrEMBL)
SYNJ2 ProteinO15056 (Uniprot-TrEMBL)
SYNJs,OCRLComplexR-HSA-1806173 (Reactome)
SYT1 ProteinP21579 (Uniprot-TrEMBL)
SYT11 ProteinQ9BT88 (Uniprot-TrEMBL)
SYT2 ProteinQ8N9I0 (Uniprot-TrEMBL)
SYT8 ProteinQ8NBV8 (Uniprot-TrEMBL)
SYT9 ProteinQ86SS6 (Uniprot-TrEMBL)
TACR1 ProteinP25103 (Uniprot-TrEMBL)
TAGs MetaboliteCHEBI:17855 (ChEBI)
TRIP10 ProteinQ15642 (Uniprot-TrEMBL)
TRIP10 dimerComplexR-HSA-8868042 (Reactome)
UBA52(1-76) ProteinP62987 (Uniprot-TrEMBL)
UBB(1-76) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(153-228) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(77-152) ProteinP0CG47 (Uniprot-TrEMBL)
UBC(1-76) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(153-228) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(229-304) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(305-380) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(381-456) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(457-532) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(533-608) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(609-684) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(77-152) ProteinP0CG48 (Uniprot-TrEMBL)
VAMP2 ProteinP63027 (Uniprot-TrEMBL)
VAMP3 ProteinQ15836 (Uniprot-TrEMBL)
VAMP7 ProteinP51809 (Uniprot-TrEMBL)
VAMP8 ProteinQ9BV40 (Uniprot-TrEMBL)
WASL,CTTNComplexR-HSA-8868228 (Reactome)
cholesterol esters MetaboliteCHEBI:17002 (ChEBI)
clathrin triskelionComplexR-HSA-8856809 (Reactome)
clathrin:HSPA8:ADPComplexR-HSA-8868617 (Reactome)
f-actin R-HSA-202986 (Reactome)
f-actinR-HSA-202986 (Reactome)
p-6Y-EGFR ProteinP00533 (Uniprot-TrEMBL)
p-AVPR2 ProteinP30518 (Uniprot-TrEMBL)
p-DVL2 ProteinO14641 (Uniprot-TrEMBL)
p-T156 AP2M1 ProteinQ96CW1 (Uniprot-TrEMBL)
p-Y371-CBL ProteinP22681 (Uniprot-TrEMBL)
p-Y850 EPS15 ProteinP42566 (Uniprot-TrEMBL)
pS-ADRB2 ProteinP07550 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
AAK1ArrowR-HSA-8871193 (Reactome)
AAK1R-HSA-8856808 (Reactome)
ADPArrowR-HSA-8856813 (Reactome)
ADPArrowR-HSA-8868066 (Reactome)
ADPArrowR-HSA-8868072 (Reactome)
AMPH:BIN1ArrowR-HSA-8869438 (Reactome)
AMPH:BIN1R-HSA-8867754 (Reactome)
AP-2 ComplexArrowR-HSA-8869438 (Reactome)
AP-2 ComplexR-HSA-8856808 (Reactome)
AP-2 ComplexR-HSA-8871196 (Reactome)
ARFGAP1:ARF6:GTPArrowR-HSA-8856808 (Reactome)
ARP2/3 complexArrowR-HSA-8869438 (Reactome)
ARP2/3 complexR-HSA-8868230 (Reactome)
ATPR-HSA-8856813 (Reactome)
ATPR-HSA-8868066 (Reactome)
ATPR-HSA-8868072 (Reactome)
CLASP proteins:cargoArrowR-HSA-8869438 (Reactome)
CLASP proteins:cargoR-HSA-8867756 (Reactome)
DNM:GDPArrowR-HSA-8869438 (Reactome)
DNM:GTPR-HSA-8868236 (Reactome)
EPS15ArrowR-HSA-8869438 (Reactome)
EPS15R-HSA-8862280 (Reactome)
FCHO1,2 dimerArrowR-HSA-8867754 (Reactome)
FCHO1,2 dimerR-HSA-8862280 (Reactome)
FNBP1 dimerArrowR-HSA-8869438 (Reactome)
FNBP1 dimerR-HSA-8867754 (Reactome)
FNBP1L dimerArrowR-HSA-8869438 (Reactome)
FNBP1L dimerR-HSA-8867754 (Reactome)
GAK,DNAJC6ArrowR-HSA-8869438 (Reactome)
GAK,DNAJC6R-HSA-8868659 (Reactome)
GGC-RAB5:GDP:GAPVD1R-HSA-8871194 (Reactome)
GGC-RAB5:GTP:GAPVD1ArrowR-HSA-8869438 (Reactome)
H2OR-HSA-8868648 (Reactome)
H2OR-HSA-8868658 (Reactome)
H2OR-HSA-8868661 (Reactome)
HIP1 dimerArrowR-HSA-8869438 (Reactome)
HIP1 dimerR-HSA-8868230 (Reactome)
HIP1R dimerArrowR-HSA-8869438 (Reactome)
HIP1R dimerR-HSA-8868230 (Reactome)
HSPA8:ATPR-HSA-8868660 (Reactome)
ITSNsArrowR-HSA-8869438 (Reactome)
ITSNsR-HSA-8862280 (Reactome)
NECAPsArrowR-HSA-8869438 (Reactome)
NECAPsR-HSA-8856808 (Reactome)
PACSIN dimersArrowR-HSA-8869438 (Reactome)
PACSIN dimersR-HSA-8867754 (Reactome)
PI(3,4)P2ArrowR-HSA-8867754 (Reactome)
PI(3,4)P2ArrowR-HSA-8868072 (Reactome)
PI(4)P:p-T156 AP-2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilinArrowR-HSA-8868658 (Reactome)
PI(4)P:p-T156 AP-2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilinArrowR-HSA-8871194 (Reactome)
PI(4)P:p-T156 AP-2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilinR-HSA-8871193 (Reactome)
PI(4)P:p-T156 AP-2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilinR-HSA-8871194 (Reactome)
PI(4)P:p-T156 AP-2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilinGGC-RAB5:GTP:GAPVD1ArrowR-HSA-8871193 (Reactome)
PI(4)P:p-T156 AP-2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilinGGC-RAB5:GTP:GAPVD1R-HSA-8869438 (Reactome)
PI(4)P:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilin:HSPA8:ATPArrowR-HSA-8868660 (Reactome)
PI(4)P:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilin:HSPA8:ATPR-HSA-8868658 (Reactome)
PI(4)P:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilin:HSPA8:ATPmim-catalysisR-HSA-8868658 (Reactome)
PI(4)P:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilinArrowR-HSA-8868659 (Reactome)
PI(4)P:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJs:auxilinR-HSA-8868660 (Reactome)
PI(4)P:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJsArrowR-HSA-8868661 (Reactome)
PI(4)P:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GDP:SYNJsR-HSA-8868659 (Reactome)
PI(4)P:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GTP:SYNJsArrowR-HSA-8868648 (Reactome)
PI(4)P:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GTP:SYNJsR-HSA-8868661 (Reactome)
PI(4)P:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GTP:SYNJsmim-catalysisR-HSA-8868661 (Reactome)
PI(4,5)P2:AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1ArrowR-HSA-8856808 (Reactome)
PI(4,5)P2:AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1R-HSA-8856813 (Reactome)
PI(4,5)P2:AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1mim-catalysisR-HSA-8856813 (Reactome)
PI(4,5)P2:AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1ArrowR-HSA-8862280 (Reactome)
PI(4,5)P2:AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1R-HSA-8856808 (Reactome)
PI(4,5)P2:AP-2:clathrinArrowR-HSA-8871196 (Reactome)
PI(4,5)P2:AP-2:clathrinR-HSA-8862280 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:PIK3C2AArrowR-HSA-8868071 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:PIK3C2AR-HSA-8867754 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:PIK3C2Amim-catalysisR-HSA-8868072 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargoArrowR-HSA-8867756 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargoR-HSA-8868071 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1ArrowR-HSA-8856813 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:FCHO1,2:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1R-HSA-8867756 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GTP:SYNJsArrowR-HSA-8868651 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GTP:SYNJsR-HSA-8868648 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GTP:SYNJsmim-catalysisR-HSA-8868648 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GTPArrowR-HSA-8868236 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimers:DNM:GTPR-HSA-8868651 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimersArrowR-HSA-8868230 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteins:ARP2/3 complex:WASL:f-actin:HIP dimersR-HSA-8868236 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteinsArrowR-HSA-8867754 (Reactome)
PI(4,5)P2:p-T156 AP-2:clathrin:ITSNs:EPS15:REPS1:SGIP1:NECAPs:AAK1:CLASP proteins:cargo:F-BAR proteins:BAR domain proteinsR-HSA-8868230 (Reactome)
PI(4,5)P2ArrowR-HSA-8868066 (Reactome)
PI(4,5)P2R-HSA-8871196 (Reactome)
PI4PArrowR-HSA-8869438 (Reactome)
PI4PR-HSA-8868066 (Reactome)
PI4PR-HSA-8868072 (Reactome)
PIK3C2AArrowR-HSA-8867754 (Reactome)
PIK3C2AR-HSA-8868071 (Reactome)
PIP5K1Cmim-catalysisR-HSA-8868066 (Reactome)
PiArrowR-HSA-8868648 (Reactome)
PiArrowR-HSA-8868658 (Reactome)
PiArrowR-HSA-8868661 (Reactome)
R-HSA-8856808 (Reactome) Recruitment of early acting proteins such as the FCHo and ITSN proteins stabilizes the transient AP-2:clathrin complex at the plasma membrane and is rapidly followed by incorporation of many more molecules of AP-2 and clathrin. AP-2 binding to the plasma-membrane enriched PI(4,5)P2 is reinforced early in the formation of a CCP by the interaction of AP-2 with PIP5K1C, which synthesizes PI(4)P to PI(4,5)P2 (Krauss et al, 2006; Bairstow et al, 2006; Thieman et al, 2009).

AP-2 recruitment is also promoted by conformational changes upon lipid and protein binding. AP-2 is a heterotetramer consisting of two large subunits (alpha and beta1 adaptin), a medium mu2 subunit and a small sigma2 subunit, and exists in a closed conformation when not part of a clathrin-coated pit (Jackson et al, 2010).
Interactions between the AP-2 mu2 subunit and PIP2 within the lipid bilayer stabilize the 'open' conformation of AP-2, exposing binding sites for cargo proteins. The open conformation is also promoted by interaction of AP-2 with early CCP proteins such as SGIP and FCHo2 (Hollopeter et al, 2014). Recruitment of clathrin stimulates the activity of AAK1, an AP-2 kinase that phosphorylates the mu2 subunit of the adaptor complex at Thr156, further stabilizing the open conformation and promoting cargo recruitment (Olusanya et al, 2001; Ricotta et al, 2002; Conner et al, 2002; Conner et al, 2003).

NECAP1 and 2 may also aid in the assembly of an emergent clathrin-coated pit. NECAP proteins have a WxxF motif at the C-terminus that binds with high affinity to the alpha-ear sandwich domain of AP-2 and an N-terminal PH ear domain that interacts both with AP-2 and a wide range of endocytic accessory proteins containing FxDxF motifs (Ritter et al, 2003; Wasiak et al, 2002; Ritter et al, 2013). Clathrin and the NECAP PH ear domain appear to compete for an AP-2 binding site. Clathrin-mediated displacement of the NECAP PH ear domain from its lower affinity AP-2 site may allow release this domain, allowing it to transition to a role in recruiting endocytic accessory proteins and cargo (Ritter et al, 2007; Ritter et al, 2013; reviewed in McMahon and Boucrot, 2011).


Finally, studies have highlighted a role for ARF6 and its GTPase activating protein ARFGAP1 in CCP formation, although the details remain to be established.
ARFGAP1 and ARF6 appear to contribute to the recruitment of some cargo, but may also play a more generalized role in CCP formation (Moravec et al, 2012; Bai et al, 2011). ARFGAP1 binds directly to AP-2 and its GAP activity is required for CME. Consistent with this, silencing of ARFGAP1 impairs CME (Schmid et al, 2006; Rawet et al 2010; Bai et al 2011). ARFGAP1 has activity towards several ARFs, including ARF6 which is found is some CCPs and is known to regulate CME under some circumstances (Moravec et al, 2003; Palacios et al, 2002; Paleotti et al, 2005; Kraus et al, 2003). ARF6 is thought to contribute to the recruitment of AP-2 and clathrin to the plasma membrane, possibly in part by affecting the lipid composition (Paleotti et al, 2002; Krauss et al, 2003).


R-HSA-8856813 (Reactome) AAK1 is a serine-threonine kinase that phosphorylates T156 of the AP2 mu2 subunit (Olusanya et al, 2001; Conner et al, 2002; Conner et al, 2003). This phosphorylation is thought to stabilize the open conformation of the AP-2 complex, exposing the cargo-binding sites and promoting cargo capture (Ricotta et al, 2002). AAK1 kinase activity is stimulated by interaction with clathrin (Conner et al, 2003; Henderson et al, 2007).
R-HSA-8862280 (Reactome) Stabilization of the transient binding of AP-2 and clathrin at the plasma membrane is effected by the recruitment of a number of early acting proteins, including FCHo (F-BAR domain-containing Fer/Cip4 homology domain-only) proteins 1 and 2, intersectins (ITSNs), EPS15, EPS15L1, REPS1 and SGIP1 among others (Henne et al, 2010; Stimpson et al, 2009; Reider et al, 2009; Dergai et al, 2010; Antonescu et al, 2011; reviewed in McMahon and Boucrot, 2011).

FCHo proteins interact with the plasma membrane-enriched PI(4,5)P2 through the F-BAR domain, which recognizes curvature in the membrane (Henne et al, 2010; Henne et al, 2007; Shimada et al, 2007; Umasankar et al, 2012). Other F-BAR proteins, such as FNBP1 and FNBP1L may join the nascent clathrin-coated pit at a slightly later stage (Shimada et al, 2007). Recruitment of EPS15 and ITSN1 and 2 appears coincident with binding of FCHo2 and depends on direct interaction with the AP2 mu homology domain of FCHo2 (Henne et al, 2010).


SGIP1 (Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1) interacts with numerous endocytic proteins including AP-2, ITSN1, REPS1, EPS15, endophilin and amphiphsyin1 and is thought to play a role in clathrin-mediated endocytosis (Trevaskis et al, 2005; Dergai et al, 2010; Uezu et al, 2007). SGIP1 is related to the FCHo proteins and is co-immunoprecipitated in a tripartite complex containing ITSN1 and REPS1 (Dergai et al, 2010). The exact function of SGIP1 in clathrin-mediated endocytosis remains to be elucidated, however recent work suggests SGIP1 and FCHo proteins may contribute to allosteric changes in AP-2 that promote membrane binding and cargo recognition (Hollopeter et al, 2014).


The recruitment of this group of early CCP proteins is rapidly followed by the incorporation of many AP-2 and clathrin molecules, stimulated in part by the FCHo- and SGIP-dependent stabilization of the open, membrane binding conformation of AP-2 (Hollopeter et al, 2014). Alternately, a proportion of the nascent CCPs may undergo abortive initiation (Loerke et al, 2009; Aguet et al, 2013; Antonescu et al, 2011). This is prompted in part through the early recruitment of the 170 kDa isoform of synaptojanin 1 (SYNJ1-170, not shown in this reaction). SYNJ1 catalyzes the hydrolysis of PI(4,5)P2 to PI(4)P and destabilizes the interaction of many early CCP components with the plasma membrane (Perera et al, 2006).
R-HSA-8867754 (Reactome) BAR (BIN/amphiphysin/Rvs) domain proteins sense and contribute to membrane curvature. BAR domain proteins generally form long, coiled-coil homo- or hetero-dimers with a concave inner surface that interacts with membranes (reviewed in Gallop and McMahon, 2005; Daumke et al, 2014). F-BAR domain proteins such as FCHo 1 and 2 recognize shallow membrane curvature and are generally recruited early in the formation of clathrin-coated pit (Itoh et al, 2005; Kamioka et al, 2004; Henne et al, 2007; Shimada et al, 2007; Henne et al, 2010). FNBP proteins and N-BAR containing endocytic proteins such as SNX9 and 18, amphiphysin (AMPH) and endophilins recognize regions of membrane with greater curvature, interact with dynamin and likely play a later role in CCP formation with spatiotemporal coupling to vesicle scission (Kamioka et al, 2004; Itoh et al, 2005; Soulet et al, 2005; Shimada et al, 2007; Shin et al, 2008; Taylor et al, 2011; reveiwed in McMahon and Boucrot, 2011). These proteins are recruited to the complex through interactions with core components of the clathrin-coated pit, and in the case of SNX9, also through interaction with PI(3,4)P2, which is generated at late stages by clathrin-associated PIK3C2A (Lundmark and Carlson, 2003; Schmid et al, 2006; Dergai et al, 2010; Brett et al, 2002 : Posor et al, 2013; reviewed in Daumke et al, 2014). Early BAR domain containing proteins such as FCHo1 and 2 are not present in either late stage clathrin-coated pits or in free clathrin-coated vesicles. Although the precise timing of their dissociation is not known, in this pathway, they are shown leaving the clathrin-coated pit upon recruitment of the more highly curved N-BAR proteins (Taylor et al, 2011).
R-HSA-8867756 (Reactome) CLASP proteins are recruited to nascent clathrin-coated pits (CCPs) through interactions with AP-2 and clathrin. Although in this pathway cargo recruitment is depicted as occuring after the recruitment of bulk AP-2 and clathrin, a number of studies suggest that they are largely recruited concomitantly (Liu et al, 2010; reviewed in McMahon and Boucrot, 2011). Concurrent interactions with sorting signals in cargo cytoplasmic tails and with clathrin and/or AP-2 ensure that CLASPs and cargo are incorporated into the emerging CCP (Schmid et al, 2006; Edeling et al, 2006; reviewed in Traub, 2009; Traub and Bonifacino, 2013; Kirchausen et al, 2014). In addition, incorporation of CLASPs and cargo may play a role in regulating the timing and dynamics of endocytosis (Loerke et al, 2009; Mettlen et al, 2009; Soohoo et al, 2013; Mettlen et al, 2010; Puthenveedu et al, 2005).
R-HSA-8868066 (Reactome) Plasma membrane enrichment of PI(4,5)P2 is maintained in part through the action of PI 4 phosphatase 5 kinases (PIPKIs) such as PIP5K1C (Di Paolo and De Camilli, 2006). PIP5K1C interacts directly with AP-2 and the interaction activates the kinase, generating a positive feedback loop for the recruitment of AP-2 to the plasma membrane (Krauss et al, 2006; Bairstow et al, 2006; Thieman et al, 2009; reviewed in Daumke et al, 2014).
R-HSA-8868071 (Reactome) PIK3C2A is a member of the class II PI 3 kinases, and phosphorylates PI(4)P to PI(3,4)P2 at the plasma membrane. PIK3C2A interacts with clathrin through a clathrin-binding domain in its unique N-terminal tail and localizes to late-stage clathrin-coated pits (Domin et al, 2000; Gaidarov et al, 2001; Gaidarov et al, 2005). Binding to clathrin stimulates the kinase activity of PIK3C2A and promotes the production of PI(3,4)P2 at the plasma membrane (Gaidarov et al, 2001). PI(3,4)P2 formation by PIK3C2A contributes to maturation of clathrin-coated pits by promoting the recruitment of BAR-domain containing proteins such as SNX9, which stimulate membrane curvature required for vesicle formation and eventual fission (Posor et al, 2013; reveiwed in Daumke et al, 2014).
R-HSA-8868072 (Reactome) Clathrin-associated PIK3C2A catalyzes the conversion of PI(4)P to PI(3,4)P2, which contributes to the recruitment of BAR domain proteins such as SNX9 to the clathrin-coated pit (Domin et al, 2000; Gaidarov et al, 2001; Gaidarov et al, 2005; Posor et al, 2013; reviewed in Daumke et al, 2014).
R-HSA-8868230 (Reactome) Actin polymerization is not absolutely required for clathrin-mediated endocytosis, and disruption of actin does not interfere with the early stages of clathrin-coated pit formation. Actin is required to complete vesicle formation under conditions of high membrane tension, such as on the apical side of polarized epithelial cell, while actin is dispensable for this process in the absence of membrane tension (Boulant et al, 2011). In cases where actin is required, it appears to be recruited late to the emerging clathrin-coated pit, just prior to or coincident with the recruitment of dynamin and vesicle scission (Taylor et al, 2011; Taylor et al, 2012; reviewed in McMahon and Boucrot, 2011). Recruitment of actin depends on the ARP2/3 complex, and cortactin or the neural Wiscott-Aldrich syndrome proteins WASL. These proteins, in turn, are recruited through interactions with N-BAR domain containing proteins such as SNX9 (Yarar et al, 2007; Shin et al, 2007; Shin et al, 2008; Ferguson et al, 2009; reviewed in Lundmark and Carlsson, 2009; McMahon and Boucrot, 2011).
HIP1 and HIP1R are additional components of the late clathrin-coated pit that interact with clathrin and AP-2 and may contribute to actin nucleation (Waelter et al, 2001; Mishra et al, 2001;Metzler et al, 2001; Legendre-Guillemin et al, 2002; Wilbur et al, 2008; Taylor et al, 2011).
R-HSA-8868236 (Reactome) Dynamin is a large GTPase whose GTP hydrolysis activity is required for the scission of clathrin-coated vesicles from the plasma membrane (reviewed in Ferguson and De Camilli, 2012). Dynamin is recruited to the plasma membrane through protein-protein interactions with many components of the clathrin-coated pit including ITSNs, SNX9 and 18 and amphiphysin (Lundmark and Carlsson, 2003; Soulet et al, 2005; David et al, 1996; Owen et al, 1998; Shupliakov et al, 1997). Although dynamin is recruited at lower levels throughout formation of the clathrin-coated pit, the bulk of dynamin is recruited at late stages, after the incorporation of BAR domain-containing proteins and actin-polymerizing factors (Ferguson et al, 2009; Taylor et al, 2011; Taylor et al, 2012; Posor et al, 2013; Meineke et al, 2013; Aguet et al, 2013; reviewed in Daumke et al, 2014). Several BAR domain proteins have SH3 domains that bind the proline rich domain (PRD) of dynamin. These interactions regulate dynamin GTPsae activity and vesicle formation (Neuman and Schmid, 2013). To facilitate scission of a clathrin-coated pit from the plasma membrane, dynamin self assembles into helical oligomers, stimulating its GTPase activity and contributing to the membrane remodeling required to form the neck of the emerging vesicle (Sweitzer and Hinshaw 1998; Yoshida et al, 2004; Chappie et al, 2010; Faelber et al, 2011; Ford et al, 2011; reviewed in McMahon and Boucrot, 2011; Daumke et al, 2014).
R-HSA-8868648 (Reactome) Inositol-5-phosphatases like SYNJs and OCRL hydrolyze PI(4,5)P2 to PI(4)P. In the context of CME, this promotes the abortive turnover (disassembly) of some CCPs, contributes to the dynamin-mediated scission of the clathrin-coated vesicle neck, and promotes clathrin uncoating following scission (Guan et al, 2010; Cremona et al, 1999; Mani et al, 2007; Chang-Ileto et al, 2011; Antonescu et al, 2011; reviewed in McMahon and Boucrot, 2011; Daumke et al, 2014).
R-HSA-8868651 (Reactome) Synaptojanin (SYNJ) 1 and 2 are inositol-5-phosphatases that sequentially convert PI(4,5)P2 to PI(4)P and PI (Cremona et al 1999; reviewed in Billcliff and Lowe, 2014). Conversion of PI(4,5)P2 to PI(4)P and PI accompanies maturation of the clathrin-coated pit, and consistent with this, SYNJ proteins are recruited to the clathrin-coated pit through interactions with a number of endocytic proteins including ITSNs, EPS15, PACSIN proteins and endophilins, as well as with clathrin and AP-2 (Haffner et al, 1997; Cestra et al, 1999; Maire et al, 2004; Schuske et al, 2003; Verstreken et al, 2003; Modregger et al, 2000; Perera et al 2006; Milosevic et al, 2011; reviewed in Dittman and Ryan, 2009). SYJN1 exists in two isoforms, a longer 170 kDA isoform and a shorter 145 kDA isoform, with slightly different roles. The recruitment and activity of SYNJ1-145 appears to largely coincide with that of dynamin at later stages of vesicle formation, while the SYNJ1-170 isoform also plays earlier roles in stabilizing the growing clathrin-coated vesicle (Perera et al, 2006; Taylor et al, 2011; Antonescu et al, 2011). SYNJ-mediated hydrolysis of PI(4,5)P2 to PI(4)P is most efficient on highly curved, endophilin-coated tubules of the vesicle neck and contributes to dynamin-mediated membrane scission (Chang-Ileto et al, 2011; reviewed in Daumke et al, 2014; McMahon and Boucrot, 2011).

In addition to SYNJ1 and 2, other inositol-5-phosphatases are also recruited to the CCP at the time of scission. These include OCRL, which is recruited through interaction with clathrin as well as the RAB5 interactor APPL1 (Erdmann et al, 2007; Mao et al, 2009; Taylor et al, 2011; Nandez et al, 2014).
R-HSA-8868658 (Reactome) HSPA8 hydrolyzes ATP to promote dissociation of the clathrin coat from the vesicle (reviewed in Sousa and Lafer, 2015). Interaction of HSPA8 with the C-terminal tail of clathrin may sterically block re-stabilization of the clathrin coat, which is thought to undergo transient cycles of 'breathing', or loosening of the interactions between the triskelions (Barouch et al, 1997; Rapoport et al, 2008; Xing et al, 2010). Alternately, HSPA8 may destabilize the clathrin coat through intermolecular collisions with the coat (reveiwed in Sousa and Lafer, 2015). The HSPA8-clathrin interaction persists once clathrin has been removed from the vesicle. This is thought to preclude aberrant repolymerization of clathrin by sequestering free clathrin (Schlossman et al, 1984; reviewed in Sousa and Lafer, 2015).
R-HSA-8868659 (Reactome) After fission from the plasma membrane, auxilin proteins DNAJC6 and GAK are recruited to the vesicle through interaction with clathrin and phosphoinositides, in particular PI4P (Greener et al, 2000; Lee et al, 2006; Massol et al, 2006; Taylor et al, 2011; Scheele et al, 2001; Fotin et al, 2004a; Fotin et al, 2004b; Guan et al, 2010; reviewed in McMahon and Boucrot, 2011; Sousa and Lafer, 2015). Auxilin in turn recruits the ATPase HSPA8 (also known as HSC70) , which uses the energy from ATP hydrolysis to remove the clathrin-coat from the vesicle, priming it for fusion with a subsequent endosomal compartment (Schlossman et al, 1984; Ungewickell et al, 1995; Rappoport et al, 2008; Xing et al, 2010; Bocking et al, 2011; Rothnie et al, 2011; reviewed in McMahon and Boucrot, 2011; Sousa and Lafer, 2015).
R-HSA-8868660 (Reactome) HSPA8 (also known as HSC70) is recruited to the clathrin-coated vesicle through interaction with DNA J proteins GAK and DNAJC6 (Rapoport et al, 2008; Xing et al, 2010; reviewed in Sousa and Lafer, 2015). Recent studies examining the stoichiometry of uncoating predict between one and three HSPA8 molecules are required per clathrin triskelion for maximal uncoating in vitro (Bocking et al, 2011; Rothnie et al, 2011). After ATP hydrolysis, HSPA8 remains associated with the liberated clathrin, which prevents aberrant repolymerization and association of clathrin (Schlossman et al, 1984; reviewed in Sousa and Lafer, 2015).
R-HSA-8868661 (Reactome) Self-assembly of dynamin around the neck of the emerging clathrin-coated vesicle stimulates its GTPase activity. This in turn promotes a conformational change in dynamin organization that is required for membrane fission (Hinshaw and Schmid, 1995; Sweitzer and Hinshaw, 1998; Takei et al, 1999; Yoshida et al, 2004; Chappie et al, 2010; Chappie et al, 2011; Ford et al, 2011; Faelber et al, 2011; reviewed in Daumke et al, 2014).
R-HSA-8869438 (Reactome) After the removal of the clathrin coat, it is likely that many of the proteins that contributed to vesicle formation are lost, although the timing and mechanism of this step are poorly understood (reviewed in McMahon and Boucrot, 2011; Lemmon, 2001).
R-HSA-8871193 (Reactome) GAPVD1 binds the alpha adaptin ear domain of AP-2 mu2, activating its RAB5-directed GEF activity and displacing AAK1. AAK1 displacement results in a net dephosphorylation of the AP-2 mu2 subunit, destabilizing the interaction of AP-2 with the vesicle membrane (Sato et al, 2005; Smerdjieva et al, 2008). In addition, RAB5 contributes to PI(4,5)P2 turnover through recruitment of a PI3K or PI phosphatase, and this also destabilizes the interaction of AP-2 with the membrane (Smerdjieva et al, 2008; Christoforidis et al, 1999; Shin et al, 2005).
R-HSA-8871194 (Reactome) RAB5 is a small GTPase that is implicated in clathrin-mediated endocytosis (Chavrier et al, 1990; McLauchlan et al, 1998; Shin et al, 2002; Taylor et al, 2011; reviewed in Stenmark, 2009; Wandiger-Ness and Zerial, 2014). Recent studies have shown that RAB5 and its associated GEF GAPVD1 may contribute to AP-2 uncoating by displacing AAK1 and promoting the net dephosphorylation of the AP-2 mu2 subunit. This is predicted to destabilize interactions with the plasma membrane and promote uncoating (Sato et al, 2005; Hunker et al, 2006; Smerdjieva et al, 2008). RAB5 and GAPVD1 also increase PI(4,5)P2 turnover, likely through recruitment of a class I PI3K or a PI phosphatase (Christoforidis et al, 1999; Shin et al, 2005).
R-HSA-8871196 (Reactome) Assembly of an endocytic clathrin-coated pit (CCP) at the plasma membrane depends on the recruitment of the AP-2 adaptor protein complex and clathrin triskelions to the lipid bilayer (reviewed in McMahon and Boucrot, 2011; Robinson, 2015). Transient interactions between the plasma membrane-enriched lipid phosphatidlyinositol 4,5-bisphosphate (PI(4,5)P2) and AP-2 initiate coated pit formation (Beck et al, 1991; Honing et al, 2005; Loerke et al, 2009; Cocucci et al, 2012). A proportion of the transient complexes between AP-2, clathrin and the plasma membrane are rapidly stabilized by the recruitment of a number of proteins, including FCHo proteins, intersectins (ITSNs), EPS15 and SGIP1 among others (Henne et al, 2010; Stimpson et al, 2009; Reider et al, 2009; Cocucci et al, 2012; reviewed in McMahon and Boucrot, 2011). Many of these early players in CCP formation bind both to the plasma membrane and to the AP-2 complex and/or clathrin.

CCP formation is a highly heterogeneous and dynamic process and includes abortive initiation of nearly half of nascent CCPs (Loerke et al, 2009; Aguet et al, 2013). Heterogeneity is in part the result of the widely varied cargo proteins, which compete for a limited number of interaction hubs on AP-2 and clatrhin and influence the other protein components of the CCPs. Heterogeneity may also be partly stochastic, or be influenced by the presence of CCP 'hot spots' in the plasma membrane (Taylor et al, 2011; Antonescu et al, 2011; Gaidarov et al, 1999; Ehrlich et al, 2004; Saffarian et al, 2009; Nunez et al, 2011). It is important to note that although events in this pathway are depicted as occuring sequentially in a defined order, in reality the assembly of a clathrin-coated vesicle may be highly variable and the temporal boundaries are likely less clearly defined. Moreover, not every CCP will have all of the proteins indicated in this pathway.
REPS1ArrowR-HSA-8869438 (Reactome)
REPS1R-HSA-8862280 (Reactome)
SGIP1ArrowR-HSA-8869438 (Reactome)
SGIP1R-HSA-8862280 (Reactome)
SH3GLsArrowR-HSA-8869438 (Reactome)
SH3GLsR-HSA-8867754 (Reactome)
SNX9,18ArrowR-HSA-8869438 (Reactome)
SNX9,18R-HSA-8867754 (Reactome)
SYNJs,OCRLArrowR-HSA-8869438 (Reactome)
SYNJs,OCRLR-HSA-8868651 (Reactome)
TRIP10 dimerArrowR-HSA-8869438 (Reactome)
TRIP10 dimerR-HSA-8867754 (Reactome)
WASL,CTTNArrowR-HSA-8869438 (Reactome)
WASL,CTTNR-HSA-8868230 (Reactome)
clathrin triskelionR-HSA-8856808 (Reactome)
clathrin triskelionR-HSA-8871196 (Reactome)
clathrin:HSPA8:ADPArrowR-HSA-8868658 (Reactome)
f-actinArrowR-HSA-8869438 (Reactome)
f-actinR-HSA-8868230 (Reactome)
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