MAP1B‐LC1 prevents autophagosome formation by linking syntaxin 17 to microtubules
| Autor: | Yuri Kurosawa, Akitsugu Yamamoto, Hiroki Inoue, Naoshi Dohmae, Kohei Arasaki, Yuichi Wakana, Shigeru Yanagi, Mitsuo Tagaya, Hana Kimura, Naoki Nishida, Haruki Nagashima |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Autophagosome Mitochondrial fission factor Protein subunit Endoplasmic Reticulum Syntaxin 17 Microtubules Biochemistry 03 medical and health sciences chemistry.chemical_compound Phosphatidylinositol Phosphates Tubulin Autophagy Genetics Humans Phosphatidylinositol Phosphorylation Molecular Biology Qa-SNARE Proteins Chemistry Endoplasmic reticulum Autophagosomes Articles Mitochondria Cell biology Phosphothreonine 030104 developmental biology Gene Knockdown Techniques Mitochondrial fission Microtubule-Associated Proteins HeLa Cells Protein Binding |
| Zdroj: | EMBO reports. 19 |
| ISSN: | 1469-3178 1469-221X |
| DOI: | 10.15252/embr.201745584 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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