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. 2015 Sep 22;6(35):37098–37116. doi: 10.18632/oncotarget.5776

Figure 2. The proposed models of CMA.

Figure 2

Substrates after partial unfolding or modification via oxidation, ubiquitination and acetylation expose the KFERQ-like motif, which can be recognized by cytosolic Cyt-HSC70. HSC70 co-chaperones are able to form complexes with Cyt-HSC70 and substrates to facilitate unfolding of these substrates and docking onto monomeric LAMP2A, which promotes the multistep organization of LAMP2A into higher-order multimeric complexes. After, Lys-HSC70 can assist the complete unfolded substrates in crossing the LAMP2A complex channel for rapid degradation in the lysosomal lumen. Then, the LAMP2A complex is disassembled into smaller complexes when substrates are no longer present. Lys-HSC90 with LAMP2A at the luminal side of the lysosomal membrane stabilizes this receptor while substrates transit between the multimeric membrane complexes.