Research Paper Volume 16, Issue 10 pp 9072—9105

Sensitivity of substrate translocation in chaperone-mediated autophagy to Alzheimer’s disease progression

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Figure 6. Substrate entry into the lysosome. Protein degradation by CMA: HSC70 recognizes the KFERQ-like motif in the substrate (step 1); the substrate-chaperone complex binds to LAMP2A (step 2); the chaperone complex expands the substrate to form the CMA translocation complex (step 3); substrate translocation is mediated by other proteins in the lysosome, when GFAP acts as a reinforcer of the complex (step 4); lysosomal protease degrades the substrate and LAMP2A dissociates from the translocation complex (step 5). Where EF1α denotes elongation factor 1-α (core subunit is EEF1A1), GFAP denotes glial fibrillary acidic protein, and HSC70 denotes heat shock cognate 71 kDa protein (also known as HSPA8).