MAP1B-LC1 prevents autophagosome formation by linking syntaxin 17 to microtubules.

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.

• Authors: Kohei Arasaki, Haruki Nagashima, Yuri Kurosawa, Hana Kimura, Naoki Nishida, Naoshi Dohmae, Akitsugu Yamamoto, Shigeru Yanagi, Yuichi Wakana, Hiroki Inoue, Mitsuo Tagaya
• Journal: EMBO reports (EMBO Rep) Vol. 19 Issue 8 (08 2018) ISSN: 1469-3178 [Electronic] England
• PMID: 29925525 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors.

Chemical References

• Microtubule-Associated Proteins
• Phosphatidylinositol Phosphates
• Qa-SNARE Proteins
• Tubulin
• microtubule-associated protein 1B
• phosphatidylinositol 3-phosphate
• Phosphothreonine

Topics

• Autophagosomes (metabolism)
• Autophagy
• Endoplasmic Reticulum (metabolism)
• Gene Knockdown Techniques
• HeLa Cells
• Humans
• Microtubule-Associated Proteins (metabolism)
• Microtubules (metabolism)
• Mitochondria (metabolism)
• Phosphatidylinositol Phosphates (metabolism)
• Phosphorylation
• Phosphothreonine (metabolism)
• Protein Binding
• Qa-SNARE Proteins (metabolism)
• Tubulin (metabolism)