WIPI1 promotes fission of endosomal transport carriers and formation of autophagosomes through distinct mechanisms.

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Version: Final published version
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Serval ID
serval:BIB_5C79F12FE465
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
WIPI1 promotes fission of endosomal transport carriers and formation of autophagosomes through distinct mechanisms.
Journal
Autophagy
Author(s)
De Leo M.G., Berger P., Mayer A.
ISSN
1554-8635 (Electronic)
ISSN-L
1554-8627
Publication state
In Press
Peer-reviewed
Oui
Pages
1-27
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Autophagosome formation requires PROPPIN/WIPI proteins and monophosphorylated phosphoinositides, such as phosphatidylinositol-3-phosphate (PtdIns3P) or PtdIns5P. This process occurs in association with mammalian endosomes, where the PROPPIN WIPI1 has additional, undefined roles in vesicular traffic. To explore whether these functions are interconnected, we dissected routes and subreactions of endosomal trafficking requiring WIPI1. WIPI1 specifically acts in the formation and fission of tubulo-vesicular endosomal transport carriers. This activity supports the PtdIns(3,5)P <sub>2</sub> -dependent transport of endosomal cargo toward the plasma membrane, Golgi, and lysosomes, suggesting a general role of WIPI1 in endosomal protein exit. Three features differentiate the endosomal and macroautophagic/autophagic activities of WIPI1: phosphoinositide binding site II, the requirement for PtdIns(3,5)P <sub>2</sub> , and bilayer deformation through a conserved amphipathic α-helix. Their inactivation preserves autophagy but leads to a strong enlargement of endosomes, which accumulate micrometer-long endosomal membrane tubules carrying cargo proteins. WIPI1 thus supports autophagy and protein exit from endosomes by different modes of action. We propose that the type of phosphoinositides occupying its two lipid binding sites, the most unusual feature of PROPPIN/WIPI family proteins, switches between these effector functions.AbbreviationsEGF: epidermal growth factorEGFR: epidermal growth factor receptorKD: knockdownKO: knockoutPtdIns3P: phosphatidylinositol-3-phosphatePtdIns5P: phosphatidylinositol-5-phosphatePtdIns(3,5)P <sub>2</sub> : phosphatidylinositol-3,5-bisphosphateTF: transferrinTFRC: transferrin receptorWT: wildtype.
Keywords
Autophagy, EGF receptor, PROPPIN, WIPI proteins, autophagosome, endosomal transport carrier, endosome, lysosome, transferrin receptor, vacuole
Pubmed
Web of science
Open Access
Yes
Create date
19/03/2021 18:19
Last modification date
26/03/2021 8:09
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