TFG binds LC3C to regulate ULK1 localization and autophagosome formation.
Autophagosomes
/ metabolism
Autophagy-Related Protein-1 Homolog
/ genetics
Blotting, Western
Fluorescent Antibody Technique
HEK293 Cells
HeLa Cells
Humans
Immunoprecipitation
Intracellular Signaling Peptides and Proteins
/ genetics
Microscopy, Electron, Transmission
Microtubule-Associated Proteins
/ genetics
Proteins
/ genetics
RNA Interference
ERGIC
LC3C
TFG
autophagy
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
17 05 2021
17 05 2021
Historique:
revised:
17
02
2021
received:
26
09
2019
accepted:
01
03
2021
pubmed:
2
5
2021
medline:
16
11
2021
entrez:
1
5
2021
Statut:
ppublish
Résumé
The early secretory pathway and autophagy are two essential and evolutionarily conserved endomembrane processes that are finely interlinked. Although growing evidence suggests that intracellular trafficking is important for autophagosome biogenesis, the molecular regulatory network involved is still not fully defined. In this study, we demonstrate a crucial effect of the COPII vesicle-related protein TFG (Trk-fused gene) on ULK1 puncta number and localization during autophagy induction. This, in turn, affects formation of the isolation membrane, as well as the correct dynamics of association between LC3B and early ATG proteins, leading to the proper formation of both omegasomes and autophagosomes. Consistently, fibroblasts derived from a hereditary spastic paraparesis (HSP) patient carrying mutated TFG (R106C) show defects in both autophagy and ULK1 puncta accumulation. In addition, we demonstrate that TFG activity in autophagy depends on its interaction with the ATG8 protein LC3C through a canonical LIR motif, thereby favouring LC3C-ULK1 binding. Altogether, our results uncover a link between TFG and autophagy and identify TFG as a molecular scaffold linking the early secretion pathway to autophagy.
Identifiants
pubmed: 33932238
doi: 10.15252/embj.2019103563
pmc: PMC8126910
doi:
Substances chimiques
Intracellular Signaling Peptides and Proteins
0
MAP1LC3C protein, human
0
Microtubule-Associated Proteins
0
Proteins
0
TFG protein, human
0
Autophagy-Related Protein-1 Homolog
EC 2.7.11.1
ULK1 protein, human
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e103563Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/B/000C0413
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/B/000C0417
Pays : United Kingdom
Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
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