Two distinct regulatory pathways govern Cct2-Atg8 binding in the process of solid aggrephagy.
EMBO Rep
; 2024 Sep 25.
Article
em En
| MEDLINE
| ID: mdl-39322741
ABSTRACT
CCT2 serves as an aggrephagy receptor that plays a crucial role in the clearance of solid aggregates, yet the underlying molecular mechanisms by which CCT2 regulates solid aggrephagy are not fully understood. Here we report that the binding of Cct2 to Atg8 is governed by two distinct regulatory mechanisms Atg1-mediated Cct2 phosphorylation and the interaction between Cct2 and Atg11. Atg1 phosphorylates Cct2 at Ser412 and Ser470, and disruption of these phosphorylation sites impairs solid aggrephagy by hindering Cct2-Atg8 binding. Additionally, we observe that Atg11, an adaptor protein involved in selective autophagy, directly associates with Cct2 through its CC4 domain. Deficiency in this interaction significantly weakens the association of Cct2 with Atg8. The requirement of Atg1-mediated Cct2 phosphorylation and of Atg11 for CCT2-LC3C binding and subsequent aggrephagy is conserved in mammalian cells. These findings provide insights into the crucial roles of Atg1-mediated Cct2 phosphorylation and Atg11-Cct2 binding as key mediators governing the interaction between Cct2 and Atg8 during the process of solid aggrephagy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
EMBO Rep
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China