RRC ID 58322
Author Arasaki K, Nagashima H, Kurosawa Y, Kimura H, Nishida N, Dohmae N, Yamamoto A, Yanagi S, Wakana Y, Inoue H, Tagaya M.
Title MAP1B-LC1 prevents autophagosome formation by linking syntaxin 17 to microtubules.
Journal EMBO Rep
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.
Volume 19(8)
Published 2018-8-1
DOI 10.15252/embr.201745584
PII embr.201745584
PMID 29925525
PMC PMC6073212
MeSH 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
IF 8.383
Times Cited 6
Resource
DNA material FLAG-MAP1B-LC1 1-243 (RDB17877) FLAG-MAP1B-LC1 1-218 (RDB17878) FLAG-MAP1B-LC1 1-207 (RDB17879) FLAG-MAP1B-LC1 T217A (RDB17880) FLAG-MAP1B-LC1 T217E (RDB17881)