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- W3113279329 abstract "Abstract Endolysosomal vesicle trafficking and autophagy are crucial degradative pathways in maintenance of cellular homeostasis. The transmembrane protein DRAM1 is a potential therapeutic target that primarily localises to endolysosomal vesicles and promotes autophagy and vesicle fusion with lysosomes. However, the molecular mechanisms underlying DRAM1-mediated vesicle fusion events remain unclear. Using high-resolution confocal microscopy in the zebrafish model, we show that mCherry-Dram1 labelled vesicles interact and fuse with early endosomes marked by PI(3)P. Following these fusion events, early endosomes mature into late endosomes in a process dependent on the conversion of PI(3)P into PI(3,5)P 2 by the lipid kinase PIKfyve. Chemical inhibition of PIKfyve reduces the targeting of Dram1 to acidic endolysosomal vesicles, arresting Dram1 in multivesicular bodies, early endosomes, or non-acidified vesicles halted in their fusion with early endosomes. In conclusion, Dram1-mediated vesicle fusion requires the formation of PI(3,5)P 2 to deliver vesicles and their cargo to the degradative environment of the lysosome." @default.
- W3113279329 created "2020-12-21" @default.
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- W3113279329 date "2020-12-15" @default.
- W3113279329 modified "2023-09-25" @default.
- W3113279329 title "DRAM1 requires PI(3,5)P2 generation by PIKfyve to deliver vesicles and their cargo to endolysosomes" @default.
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- W3113279329 doi "https://doi.org/10.1101/2020.12.15.422832" @default.
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