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 glial fibrillary acidic protein (GFAP) and elongation factor 1α (EEF1A1). During autophagy, a phosphorylated version of GFAP remains bound to EEF1A1. When GTP becomes available, EEF1A1 dissociates from GFAP and binds with GTP in the cytosol. This makes p-GFAP available to bind with GFAP in the LAMP2a multimer complex. Consequently, p-GFAP sequesters GFAP from LAMP2a multimer (Bandyopadhyay U et al. 2010). Experiments confirming this event were performed in rats.
Cuervo, AM, Kiffin, R, Sridhar, S, Kaushik, S, Bandyopadhyay, U
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