Unfolded substrate in LAMP2a multimeric complex binds HSPA8

Stable Identifier
Homo sapiens
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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 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.

Literature References
PubMed ID Title Journal Year
9151685 An intralysosomal hsp70 is required for a selective pathway of lysosomal protein degradation

Dice, JF, Agarraberes, FA, Terlecky, SR

J. Cell Biol. 1997
9038169 A population of rat liver lysosomes responsible for the selective uptake and degradation of cytosolic proteins

Dice, JF, Cuervo, AM, Knecht, E

J. Biol. Chem. 1997
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