CALCOCO1 acts with VAMP-associated proteins to mediate ER-phagy.
EMBO J
; 39(15): e103649, 2020 08 03.
Article
em En
| MEDLINE
| ID: mdl-32525583
ABSTRACT
The endoplasmic reticulum (ER) plays important roles in protein synthesis and folding, and calcium storage. The volume of the ER and expression of its resident proteins are increased in response to nutrient stress. ER-phagy, a selective form of autophagy, is involved in the degradation of the excess components of the ER to restore homeostasis. Six ER-resident proteins have been identified as ER-phagy receptors so far. In this study, we have identified CALCOCO1 as a novel ER-phagy receptor for the degradation of the tubular ER in response to proteotoxic and nutrient stress. CALCOCO1 is a homomeric protein that binds directly to ATG8 proteins via LIR- and UDS-interacting region (UIR) motifs acting co-dependently. CALCOCO1-mediated ER-phagy requires interaction with VAMP-associated proteins VAPA and VAPB on the ER membranes via a conserved FFAT-like motif. Depletion of CALCOCO1 causes expansion of the ER and inefficient basal autophagy flux. Unlike the other ER-phagy receptors, CALCOCO1 is peripherally associated with the ER. Therefore, we define CALCOCO1 as a soluble ER-phagy receptor.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Autofagia
/
Fatores de Transcrição
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Proteínas de Ligação ao Cálcio
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Proteínas de Transporte Vesicular
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Membranas Intracelulares
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Noruega