Reactome | Substrate:LAMP2a:HSP90 polymerizes

Substrate:LAMP2a:HSP90 polymerizes

Stable Identifier

R-HSA-9624158

Type

Reaction [transition]

Species

Homo sapiens

Compartment

lysosomal lumen, lysosomal membrane

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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.

Literature References

PubMed ID	Title	Journal	Year
20797626	Identification of regulators of chaperone-mediated autophagy Bandyopadhyay, U, Sridhar, S, Kaushik, S, Kiffin, R, Cuervo, AM	Mol. Cell	2010
18644871	The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane Bandyopadhyay, U, Kaushik, S, Varticovski, L, Cuervo, AM	Mol. Cell. Biol.	2008