Proposed model of 6-OHDA-induced autophagy-based unconventional PARK7 secretion. (IMAGE)
Caption
Oxidative stress induced by 6-OHDA stimulates autophagy flux, which enhances STX17-mediated autolysosome formation, leading to the degradation of autophagosomal contents. However, in response to autophagy promotion by 6-OHDA, a subset of autophagosomes recruits ERGIC R-SNARE SEC22B. The KFERQ-like motifs of monomeric PARK7 selectively bind to HSPA8 chaperones and are recruited to the lysosomal membrane, followed by translocation into the lysosomal lumen via the LAMP2 channel. A pool of PARK7-containing lysosomes fuses with SEC22B-containing autophagosomes to form secretory autolysosomes, which then fuse with the plasma membrane mediated by a unique QabcR–SNARE complex comprising STX3/4, VTI1B, STX8, and SEC22B, releasing PARK7 into the extracellular matrix.
Credit
Dr. Biplab Kumar Dash from Doshisha University, Japan
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License
CC BY-NC-ND