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 |
7.497
|
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) |
Human and Animal Cells |
HeLa(RCB0007) |