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.
Cuervo, AM, Dice, JF
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