Nephrin family interactions (Homo sapiens)

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1-817-217, 29-3122-2422, 2511, 13-1515, 162, 3, 9-1226-28cytosolFYNPodocin:p-Nephrin:Fyn:NEPH1IQGAP1N-WASPNephrin dimer:IQGAP1CD2APNephrin dimerPI3K:CD2AP:p-Nephrin:Fyn:NEPH1CASKNEPH1:p-Nephrin:Fyn:NCK:N-WASPNephrin dimer:CASKADPPI3KCD2AP:p-Nephrin:Fyn:NEPH1adherens junction-associated proteinsATPNEPH1:p-Nephrin:Fyn:NCKNephrin dimer:NEPH1NEPH1Podocin oligomerNephrinNEPH1:p-Nephrin:FynNephrin dimer:adherins junction-associated proteinsNCKNephrin dimer:NEPH2/NEPH3NEPH2/NEPH3


Description

Nephrin is a member of the Super-IgG-Molecule family and is most prominently expressed in kidney podocytes. It is a major if not the most important structural component of the slit diaphragm, a modified adherens junction in between these cells. Nephrin is composed of an extracellular domain with eight distal IgG like domains and one proximal fibronectin type III domain, a transmembrane domain and a short intracellular domain. Nephrin molecules show both homophilic and heterophilic interactions. Among heterophilic interaction partners slit diaphragm proteins such as NEPH1, NEPH2 and NEPH3 were shown to stabilize the slit diaphragm structure. Intracellularly Podocin, CD2 associated protein (CD2AP) and adherins junction associated proteins like IQGAP, MAGI, CASK and spectrins were all shown to interact with nephrin. Hence nephrin seems to play a major role in organizing the molecular structure of the slit diaphragm itself and via its binding partners links it to the actin cytoskeleton. Nephrin does not only fulfill static properties within the slit diaphragm but by tyrosine phosphorylation of its cytoplasmic tail by the Src kinase Fyn it initiates the PI3K AKT signaling cascade which seems to promote antiapoptotic signals.

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Bibliography

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  1. Tryggvason K.; ''Unraveling the mechanisms of glomerular ultrafiltration: nephrin, a key component of the slit diaphragm.''; PubMed Europe PMC Scholia
  2. Garg P, Verma R, Nihalani D, Johnstone DB, Holzman LB.; ''Neph1 cooperates with nephrin to transduce a signal that induces actin polymerization.''; PubMed Europe PMC Scholia
  3. Li H, Lemay S, Aoudjit L, Kawachi H, Takano T.; ''SRC-family kinase Fyn phosphorylates the cytoplasmic domain of nephrin and modulates its interaction with podocin.''; PubMed Europe PMC Scholia
  4. Neumann-Haefelin E, Kramer-Zucker A, Slanchev K, Hartleben B, Noutsou F, Martin K, Wanner N, Ritter A, Gödel M, Pagel P, Fu X, Müller A, Baumeister R, Walz G, Huber TB.; ''A model organism approach: defining the role of Neph proteins as regulators of neuron and kidney morphogenesis.''; PubMed Europe PMC Scholia
  5. Huber TB, Kottgen M, Schilling B, Walz G, Benzing T.; ''Interaction with podocin facilitates nephrin signaling.''; PubMed Europe PMC Scholia
  6. Schwarz K, Simons M, Reiser J, Saleem MA, Faul C, Kriz W, Shaw AS, Holzman LB, Mundel P.; ''Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin.''; PubMed Europe PMC Scholia
  7. Zhu J, Sun N, Aoudjit L, Li H, Kawachi H, Lemay S, Takano T.; ''Nephrin mediates actin reorganization via phosphoinositide 3-kinase in podocytes.''; PubMed Europe PMC Scholia
  8. Lehtonen S, Ryan JJ, Kudlicka K, Iino N, Zhou H, Farquhar MG.; ''Cell junction-associated proteins IQGAP1, MAGI-2, CASK, spectrins, and alpha-actinin are components of the nephrin multiprotein complex.''; PubMed Europe PMC Scholia
  9. Lehtonen S, Lehtonen E, Kudlicka K, Holthöfer H, Farquhar MG.; ''Nephrin forms a complex with adherens junction proteins and CASK in podocytes and in Madin-Darby canine kidney cells expressing nephrin.''; PubMed Europe PMC Scholia
  10. Huber TB, Benzing T.; ''The slit diaphragm: a signaling platform to regulate podocyte function.''; PubMed Europe PMC Scholia
  11. Ruotsalainen V, Ljungberg P, Wartiovaara J, Lenkkeri U, Kestilä M, Jalanko H, Holmberg C, Tryggvason K.; ''Nephrin is specifically located at the slit diaphragm of glomerular podocytes.''; PubMed Europe PMC Scholia
  12. Verma R, Wharram B, Kovari I, Kunkel R, Nihalani D, Wary KK, Wiggins RC, Killen P, Holzman LB.; ''Fyn binds to and phosphorylates the kidney slit diaphragm component Nephrin.''; PubMed Europe PMC Scholia
  13. Rohatgi R, Nollau P, Ho HY, Kirschner MW, Mayer BJ.; ''Nck and phosphatidylinositol 4,5-bisphosphate synergistically activate actin polymerization through the N-WASP-Arp2/3 pathway.''; PubMed Europe PMC Scholia
  14. Verma R, Kovari I, Soofi A, Nihalani D, Patrie K, Holzman LB.; ''Nephrin ectodomain engagement results in Src kinase activation, nephrin phosphorylation, Nck recruitment, and actin polymerization.''; PubMed Europe PMC Scholia
  15. Tryggvason K, Patrakka J, Wartiovaara J.; ''Hereditary proteinuria syndromes and mechanisms of proteinuria.''; PubMed Europe PMC Scholia
  16. Lahdenperä J, Kilpeläinen P, Liu XL, Pikkarainen T, Reponen P, Ruotsalainen V, Tryggvason K.; ''Clustering-induced tyrosine phosphorylation of nephrin by Src family kinases.''; PubMed Europe PMC Scholia
  17. Huber TB, Hartleben B, Kim J, Schmidts M, Schermer B, Keil A, Egger L, Lecha RL, Borner C, Pavenstädt H, Shaw AS, Walz G, Benzing T.; ''Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling.''; PubMed Europe PMC Scholia
  18. Liu XL, Kilpeläinen P, Hellman U, Sun Y, Wartiovaara J, Morgunova E, Pikkarainen T, Yan K, Jonsson AP, Tryggvason K.; ''Characterization of the interactions of the nephrin intracellular domain.''; PubMed Europe PMC Scholia
  19. Liu G, Kaw B, Kurfis J, Rahmanuddin S, Kanwar YS, Chugh SS.; ''Neph1 and nephrin interaction in the slit diaphragm is an important determinant of glomerular permeability.''; PubMed Europe PMC Scholia
  20. Jones N, New LA, Fortino MA, Eremina V, Ruston J, Blasutig IM, Aoudjit L, Zou Y, Liu X, Yu GL, Takano T, Quaggin SE, Pawson T.; ''Nck proteins maintain the adult glomerular filtration barrier.''; PubMed Europe PMC Scholia
  21. Zenker M, Machuca E, Antignac C.; ''Genetics of nephrotic syndrome: new insights into molecules acting at the glomerular filtration barrier.''; PubMed Europe PMC Scholia
  22. Khoshnoodi J, Sigmundsson K, Ofverstedt LG, Skoglund U, Obrink B, Wartiovaara J, Tryggvason K.; ''Nephrin promotes cell-cell adhesion through homophilic interactions.''; PubMed Europe PMC Scholia
  23. Patrakka J, Tryggvason K.; ''Nephrin--a unique structural and signaling protein of the kidney filter.''; PubMed Europe PMC Scholia
  24. Tryggvason K, Pikkarainen T, Patrakka J.; ''Nck links nephrin to actin in kidney podocytes.''; PubMed Europe PMC Scholia
  25. Gerke P, Sellin L, Kretz O, Petraschka D, Zentgraf H, Benzing T, Walz G.; ''NEPH2 is located at the glomerular slit diaphragm, interacts with nephrin and is cleaved from podocytes by metalloproteinases.''; PubMed Europe PMC Scholia
  26. Wartiovaara J, Ofverstedt LG, Khoshnoodi J, Zhang J, Mäkelä E, Sandin S, Ruotsalainen V, Cheng RH, Jalanko H, Skoglund U, Tryggvason K.; ''Nephrin strands contribute to a porous slit diaphragm scaffold as revealed by electron tomography.''; PubMed Europe PMC Scholia
  27. Aaltonen P, Holthöfer H.; ''The nephrin-based slit diaphragm: new insight into the signalling platform identifies targets for therapy.''; PubMed Europe PMC Scholia
  28. Huber TB, Simons M, Hartleben B, Sernetz L, Schmidts M, Gundlach E, Saleem MA, Walz G, Benzing T.; ''Molecular basis of the functional podocin-nephrin complex: mutations in the NPHS2 gene disrupt nephrin targeting to lipid raft microdomains.''; PubMed Europe PMC Scholia
  29. Jones N, Blasutig IM, Eremina V, Ruston JM, Bladt F, Li H, Huang H, Larose L, Li SS, Takano T, Quaggin SE, Pawson T.; ''Nck adaptor proteins link nephrin to the actin cytoskeleton of kidney podocytes.''; PubMed Europe PMC Scholia
  30. Li S, Wang Q, Chakladar A, Bronson RT, Bernards A.; ''Gastric hyperplasia in mice lacking the putative Cdc42 effector IQGAP1.''; PubMed Europe PMC Scholia
  31. Gerke P, Huber TB, Sellin L, Benzing T, Walz G.; ''Homodimerization and heterodimerization of the glomerular podocyte proteins nephrin and NEPH1.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114888view16:40, 25 January 2021ReactomeTeamReactome version 75
113334view11:40, 2 November 2020ReactomeTeamReactome version 74
112545view15:51, 9 October 2020ReactomeTeamReactome version 73
101459view11:32, 1 November 2018ReactomeTeamreactome version 66
100997view21:11, 31 October 2018ReactomeTeamreactome version 65
100533view19:45, 31 October 2018ReactomeTeamreactome version 64
100080view16:30, 31 October 2018ReactomeTeamreactome version 63
99631view15:01, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99237view12:44, 31 October 2018ReactomeTeamreactome version 62
94496view09:02, 14 September 2017Mkutmonreactome version 61
88033view13:34, 25 July 2016RyanmillerOntology Term : 'signaling pathway' added !
86623view09:22, 11 July 2016ReactomeTeamreactome version 56
83128view10:03, 18 November 2015ReactomeTeamVersion54
81468view13:00, 21 August 2015ReactomeTeamVersion53
76942view08:21, 17 July 2014ReactomeTeamFixed remaining interactions
76647view12:01, 16 July 2014ReactomeTeamFixed remaining interactions
75977view10:03, 11 June 2014ReactomeTeamRe-fixing comment source
75680view11:00, 10 June 2014ReactomeTeamReactome 48 Update
75035view13:54, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74679view08:44, 30 April 2014ReactomeTeamReactome46
42085view21:55, 4 March 2011MaintBotAutomatic update
39893view05:55, 21 January 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ADP Metabolite16761 (ChEBI)
ATP Metabolite15422 (ChEBI)
CASK ProteinO14936 (UniProt)
CD2AP ProteinQ9Y5K6 (UniProt)
CD2AP:p-Nephrin:

Fyn:NEPH1

ComplexREACT_24742 (Reactome)
FYN ProteinP06241 (UniProt)
IQGAP1 ProteinP46940 (UniProt)
N-WASP ProteinO00401 (UniProt)
NCK ProteinREACT_17190 (Reactome)
NEPH1 ProteinQ96J84 (UniProt)
NEPH1:p-Nephrin:

Fyn

ComplexREACT_24538 (Reactome)
NEPH1:p-Nephrin:

Fyn:NCK

ComplexREACT_24581 (Reactome)
NEPH1:p-Nephrin:

Fyn:NCK:N-WASP

ComplexREACT_24683 (Reactome)
NEPH2/NEPH3 ProteinREACT_24799 (Reactome)
Nephrin ProteinO60500-1 (UniProt)
Nephrin dimer ComplexREACT_24735 (Reactome)
Nephrin dimer:

IQGAP1

ComplexREACT_24686 (Reactome)
Nephrin dimer:

NEPH1

ComplexREACT_24342 (Reactome)
Nephrin dimer:

NEPH2/NEPH3

ComplexREACT_24383 (Reactome)
Nephrin dimer:

adherins junction- associated proteins

ComplexREACT_24676 (Reactome)
Nephrin dimer:CASK ComplexREACT_24544 (Reactome)
PI3K ComplexREACT_4240 (Reactome)
PI3K:CD2AP:p-

Nephrin:Fyn:NEPH1

ComplexREACT_24519 (Reactome)
Podocin oligomer UnknownREACT_24198 (Reactome)
Podocin:p-Nephrin:

Fyn:NEPH1

ComplexREACT_24571 (Reactome)
adherens junction-

associated proteins

ProteinREACT_24771 (Reactome)

Annotated Interactions

No annotated interactions

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