MAP1B‐LC1 prevents autophagosome formation by linking syntaxin 17 to microtubules |
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| Authors: | Kohei Arasaki Yuri Kurosawa Hana Kimura Naoki Nishida Naoshi Dohmae Akitsugu Yamamoto Shigeru Yanagi Yuichi Wakana Hiroki Inoue Mitsuo Tagaya |
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| Affiliation: | 1. School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, JapanThese authors contributed equally to this work;2. School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan;3. Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama, Japan;4. Faculty of Bioscience, Nagahama Institute of Bio‐Science and Technology, Nagahama, Shiga, Japan |
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| Abstract: | In fed cells, syntaxin 17 (Stx17) is associated with microtubules at the endoplasmic reticulum–mitochondria interface and promotes mitochondrial fission by determining the localization and function of the mitochondrial fission factor Drp1. Upon starvation, Stx17 dissociates from microtubules and Drp1, and binds to Atg14L, a subunit of the phosphatidylinositol 3‐kinase complex, to facilitate phosphatidylinositol 3‐phosphate production and thereby autophagosome formation, but the mechanism underlying this phenomenon remains unknown. Here we identify MAP1B‐LC1 (microtubule‐associated protein 1B‐light chain 1) as a critical regulator of Stx17 function. Depletion of MAP1B‐LC1 causes Stx17‐dependent autophagosome accumulation even under nutrient‐rich conditions, whereas its overexpression blocks starvation‐induced autophagosome formation. MAP1B‐LC1 links microtubules and Stx17 in fed cells, and starvation causes the dephosphorylation of MAP1B‐LC1 at Thr217, allowing Stx17 to dissociate from MAP1B‐LC1 and bind to Atg14L. Our results reveal the mechanism by which Stx17 changes its binding partners in response to nutrient status. |
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| Keywords: | Atg14L autophagy MAP1B‐LC1 microtubules syntaxin 17 |
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