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

EMBO Rep. 2018 Aug;19(8):e45584. doi: 10.15252/embr.201745584. Epub 2018 Jun 19.

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.

Keywords: Atg14L; MAP1B‐LC1; autophagy; microtubules; syntaxin 17.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

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