In contrary to the vesicle-mediated macroautophagy, the chaperone mediated mechanism of autophagy selectively targets individual proteins to the lysosome for degradation. Chaperones bind intracellular proteins based on recognition motifs and transports them from the cytosol to the lysosomal membrane. Subsequently, the protein is translocated into the lumen for digestion (Cuervo A M et al. 2014, Kaushik S et al. 2018).
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Cuervo AM, Wong E.; ''Chaperone-mediated autophagy: roles in disease and aging.''; PubMedEurope PMCScholia
Kaushik S, Cuervo AM.; ''Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy facilitates lipolysis.''; PubMedEurope PMCScholia
Cuervo AM, Dice JF.; ''Unique properties of lamp2a compared to other lamp2 isoforms.''; PubMedEurope PMCScholia
Bandyopadhyay U, Sridhar S, Kaushik S, Kiffin R, Cuervo AM.; ''Identification of regulators of chaperone-mediated autophagy.''; PubMedEurope PMCScholia
Cuervo AM, Dice JF, Knecht E.; ''A population of rat liver lysosomes responsible for the selective uptake and degradation of cytosolic proteins.''; PubMedEurope PMCScholia
Arias E, Koga H, Diaz A, Mocholi E, Patel B, Cuervo AM.; ''Lysosomal mTORC2/PHLPP1/Akt Regulate Chaperone-Mediated Autophagy.''; PubMedEurope PMCScholia
Agarraberes FA, Terlecky SR, Dice JF.; ''An intralysosomal hsp70 is required for a selective pathway of lysosomal protein degradation.''; PubMedEurope PMCScholia
Kaushik S, Bandyopadhyay U, Sridhar S, Kiffin R, Martinez-Vicente M, Kon M, Orenstein SJ, Wong E, Cuervo AM.; ''Chaperone-mediated autophagy at a glance.''; PubMedEurope PMCScholia
Dice JF.; ''Peptide sequences that target cytosolic proteins for lysosomal proteolysis.''; PubMedEurope PMCScholia
Bandyopadhyay U, Kaushik S, Varticovski L, Cuervo AM.; ''The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane.''; PubMedEurope PMCScholia
Chiang HL, Terlecky SR, Plant CP, Dice JF.; ''A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins.''; PubMedEurope PMCScholia
Kaushik S, Cuervo AM.; ''The coming of age of chaperone-mediated autophagy.''; PubMedEurope PMCScholia
Cuervo AM, Dice JF.; ''A receptor for the selective uptake and degradation of proteins by lysosomes.''; PubMedEurope PMCScholia
Intracellular proteins are targeted for proteolytic degradation in the lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) acts as the constitutive chaperone that binds substrate proteins in the cytosol. HSPA8 recognizes a motif based on the charge of the amino acids (Chiang H et al. 1989, Dice JF et al. 1990). This allows the motif to have multiple sequence possibilities and also create a motif through post-translational modifications such as phosphorylation and acetylation. Once bound with HSPA8, the substrates are targeted to the lysosome or endosome.
Intracellular proteins are targeted for proteolytic degradation in lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) acts as the constitutive chaperone that binds substrates in the cytosol. Consequently, the Hspa8:Substrate complex translocates from cytosol to lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a) (Cuervo AM and Dice JF. 1996). Four positively charged amino acids in the cytosolic tail of the LAMP2a isoform is known to regulate the binding mechanism (Cuervo AM and Dice JF. 2000). Experiments confirming this binding were performed on rat models.
Heat shock cognate 71 kDa protein (HSPA8) translocates substrates from cytosol to lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a). HSPA8 is then released from this complex. Subsequently, Heat shock protein HSP 90 binds to the lysosomal luminal end of LAMP2a (Bandyopadhyay U et al. 2008). This facilitates the multimerization of LAMP2a and internalization of substrate into the lumen. Experiments confirming this binding were performed on rat models.
Intracellular proteins are targeted for proteolytic degradation in lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) acts as the constitutive chaperone that binds KFERQ-domain containing substrates in the cytosol. Consequently, the Hspa8:Substrate complex translocates from the cytosol to the lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a). Post-binding, HSPA8 is released from the complex to allow multimerization of LAMP2a and internalization of the substrate (Bandyopadhyay U et al. 2008). Experiments confirming this binding were performed on rat models.
Intracellular proteins are targeted for proteolytic degradation in the lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) acts as the constitutive chaperone that binds KFERQ-domain containing substrates in the cytosol. Consequently, the Hspa8:Substrate complex translocates from cytosol to lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a). Subsequently, HSPA8 is released and Heat shock protein HSP 90 binds to the lysosomal luminal end of LAMP2a. Binding of HSP90 stabilizes LAMP2 to multimerize into a 700 kDa complex (Bandyopadhyay U et al. 2008). This facilitates the internalization of substrate into the lumen. Experiments confirming this binding were performed on rat models.
Heat shock cognate 71 kDa protein (HSPA8) translocates substrates from the cytosol to the lysosomal membrane. Subsequently, the substrate unfolds and binds to HSPA8 in the lysosomal lumen. HSPA8 facilitates the transport of the unfolded substrate to the lumen where it is then degraded (Agarraberes FA et al. 1997, Cuervo AM et al. 1997).
Intracellular proteins are targeted for proteolytic degradation in the lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) acts as the constitutive chaperone that binds a KFERQ-domain containing substrate in the cytosol and translocates to lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a). Subsequently, Hspa8 is released and Heat shock protein HSP90 binds to the lysosomal luminal end of LAMP2a. The LAMP2a complex then multimerizes and stabilizes. Now, the substrate unfolds and binds to HSPA8 in the lysosomal lumen (Agarraberes FA et al. 1997, Cuervo AM et al. 1997). Subsequently, the substrate is internalized and degraded in the lumen. Experiments confirming this interaction were performed in rats.
Intracellular proteins are targeted for proteolytic degradation in the lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) acts as the constitutive chaperone that binds KFERQ-domain containing substrates in the cytosol. Consequently, the HSPA8:Substrate complex translocates from cytosol to lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a). Subsequently, HSPA8 is released and Heat shock protein HSP 90 binds to the lysosomal luminal end of LAMP2a. This LAMP2a complex then multimerizes into a 700 kDa entity and is stabilized by the binding of Glial fibrillary acidic protein (GFAP) (Bandyopadhyay U et al. 2010). Subsequently, the substrate is unfolded and internalized into the lumen. Experiments confirming this binding were performed on rat models.
Intracellular proteins are targeted for proteolytic degradation in lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) transports substrates from the cytosol to the lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a). Subsequently, LAMP2a forms a multimeric complex stabilized with the aid of HSP90 and glial fibrillary acidic protein (GFAP). This multimer allows the transfer of substrate into the lumen. The stability of this complex is regulated by the dynamics of GFAP and elongation factor 1α (EEF1A1). During autophagy, a phosphorylated version of GFAP remains bound to EEF1A1. When GTP becomes available, EEF1A1 dissociates from GFAP (Bandyopadhyay U et al. 2010). Experiments confirming this binding were performed in rats.
Intracellular proteins are targeted for proteolytic degradation in lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) transports substrates from the cytosol to the lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a). Subsequently, LAMP2a forms a multimeric complex stabilized with the aid of HSP90 and glial fibrillary acidic protein (GFAP). This multimer allows the transfer of substrate into the lumen. The stability of this complex is regulated by the dynamics of GFAP and elongation factor 1α (EEF1A1). During autophagy, a phosphorylated version of GFAP remains bound to EEF1A1. When GTP becomes available, Eef1a1 dissociates from GFAP and binds with GTP in the cytosol (Bandyopadhyay U et al. 2010). Experiments confirming this binding were performed in rats.
Intracellular proteins are targeted for proteolytic degradation in lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) transports substrates from the cytosol to the lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a). Subsequently, LAMP2a forms a multimeric complex stabilized with the aid of HSP90 and glial fibrillary acidic protein (GFAP). This multimer allows the transfer of substrate into the lumen. The stability of this complex is regulated by the dynamics of GFAP and elongation factor 1α (EEF1A1). During autophagy, a phosphorylated version of GFAP remains bound to EEF1A1. When GTP becomes available, EEF1A1 dissociates from GFAP and binds with GTP in the cytosol. Subsequently, EEF1A1 is translocated from lysosomal membrane to cytosol. This makes p-GFAP available to bind with GFAP in the LAMP2a multimer complex (Bandyopadhyay U et al. 2010). Experiments confirming this binding were performed in rats.
Intracellular proteins are targeted for proteolytic degradation in lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) transports substrates from the cytosol to the lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a). Subsequently, LAMP2a forms a multimeric complex stabilized with the aid of HSP90 and glial fibrillary acidic protein (GFAP). This multimer allows the transfer of substrate into the lumen. The stability of this complex is regulated by the dynamics of GFAP and elongation factor 1α (EEF1A1). During autophagy, a phosphorylated version of GFAP remains bound to EEF1A1 (Bandyopadhyay U et al. 2010, Arias E et al. 2015). Experiments confirming this binding were performed in rats.
Heat shock cognate 71 kDa protein (HSPA8) translocates substrates from the cytosol to the lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a). The LAMP2a complex then multimerizes and stabilizes. Subsequently, the substrate unfolds and translocates to the lumen. The substrate bound HSPA8 then dissociates from LAMP2a multimer (Agarraberes FA et al. 1997, Cuervo AM et al. 1997). The function of LAMP2a multimer is now complete and starts to disassemble.
Intracellular proteins are targeted for proteolytic degradation in lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) transports substrates from the cytosol to the lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a). Subsequently, LAMP2a forms a multimeric complex stabilized with the aid of HSP90 and glial fibrillary acidic protein (GFAP). This multimer allows the transfer of substrate into the lumen. The stability of this complex is regulated by the dynamics of GFAP and elongation factor 1α (EEF1A1). During autophagy, a phosphorylated version of GFAP remains bound to EEF1A1. When GTP becomes available, EEF1A1 dissociates from GFAP and binds with GTP in the cytosol. Subsequently, EEF1A1 is translocated from lysosomal membrane to cytosol (Bandyopadhyay U et al. 2010). Experiments confirming this binding were performed in rats.
Intracellular proteins are targeted for proteolytic degradation in lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) transports substrates from the cytosol to the lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a). Subsequently, LAMP2a forms a multimeric complex and transfers the substrate into the lumen. The stability of this complex is regulated by the dynamics of HSPA8. Cytosolic HSPA8 binds with LAMP2a multimers in the lysosomal membrane and triggers their disassembly into monomeric units (Bandyopadhyay U et al. 2008). HSPA8 dissociates from LAMP2a to make it available for further substrate autophagy. Experiments related to this event were performed in rats.
Intracellular proteins are targeted for proteolytic degradation in lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) transports substrates from the cytosol to the lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a). Subsequently, LAMP2a forms a multimeric complex and transfers the substrate into the lumen. The stability of this complex is regulated by the dynamics of glial fibrillary acidic protein (GFAP) and elongation factor 1α (EEF1A1). During autophagy, a phosphorylated version of GFAP remains bound to EEF1A1. When GTP becomes available, EEF1A1 dissociates from GFAP and binds with GTP in the cytosol. This makes p-GFAP available to bind with GFAP in the LAMP2a multimer complex. Consequently, p-GFAP sequesters GFAP from LAMP2a multimer (Bandyopadhyay U et al. 2010). Experiments confirming this event were performed in rats.
Intracellular proteins are targeted for proteolytic degradation in lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) transports substrates from the cytosol to the lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a). Subsequently, LAMP2a forms a multimeric complex and transfers the substrate into the lumen. The stability of this complex is regulated by the dynamics of HSPA8. Cytosolic HSPA8 binds with LAMP2a multimers in the lysosomal membrane and triggers their disassembly. Interestingly, substrate bound HSPA8 do not have this effect on LAMP2a (Bandyopadhyay U et al. 2008). Experiments confirming this event were performed in rats.
Intracellular proteins are targeted for proteolytic degradation in lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) transports substrates from the cytosol to the lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a). Subsequently, LAMP2a forms a multimeric complex and transfers the substrate into the lumen. The stability of this complex is regulated by the dynamics of HSPA8. Cytosolic HSPA8 binds with LAMP2a multimers in the lysosomal membrane. This triggers the disassembly of multimeric complexes into monomeric units (Bandyopadhyay U et al. 2008). Experiments confirming this event were performed in rats.
Intracellular proteins are targeted for proteolytic degradation in lysosome with the aid of chaperones. Heat shock cognate 71 kDa protein (HSPA8) transports substrates from the cytosol to the lysosomal membrane where it binds to Lysosome-associated membrane glycoprotein 2 (LAMP2a). Subsequently, LAMP2a forms a multimeric complex and transfers the substrate into the lumen. The stability of this complex is regulated by the dynamics of Heat shock protein HSP 90 (HSP90) and HSPA8 (Bandyopadhyay U et al. 2008). HSPA8 and HSP90 dissociate from LAMP2a to make it available for further substrate autophagy. Experiments related to this event were performed in rats.
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autophagic
substrateschaperone mediated
autophagyAnnotated Interactions
autophagic
substratesautophagic
substrateschaperone mediated
autophagy