Substrate:LAMP2a:HSP90 polymerizes

Stable Identifier
R-HSA-9624158
Type
Reaction [transition]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
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
18644871 The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane

Cuervo, AM, Kaushik, S, Bandyopadhyay, U, Varticovski, L

Mol. Cell. Biol. 2008
20797626 Identification of regulators of chaperone-mediated autophagy

Cuervo, AM, Kiffin, R, Sridhar, S, Kaushik, S, Bandyopadhyay, U

Mol. Cell 2010
Participants
Participates
Inferred From
Authored
Reviewed
Created
Cite Us!