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