TFG binds LC3C to regulate ULK1 localization and autophagosome formation.
EMBO J
; 40(10): e103563, 2021 05 17.
Article
em En
| MEDLINE
| ID: mdl-33932238
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas
/
Peptídeos e Proteínas de Sinalização Intracelular
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Autofagossomos
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Proteína Homóloga à Proteína-1 Relacionada à Autofagia
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Proteínas Associadas aos Microtúbulos
Limite:
Humans
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Itália