A Zn2+-triggered two-step mechanism of CLIC1 membrane insertion and activation into chloride channels.
J Cell Sci
; 135(15)2022 08 01.
Article
em En
| MEDLINE
| ID: mdl-35833483
ABSTRACT
The chloride intracellular channel (CLIC) protein family displays the unique feature of altering its structure from a soluble form to a membrane-bound chloride channel. CLIC1, a member of this family, is found in the cytoplasm or in internal and plasma membranes, with membrane relocalisation linked to endothelial disfunction, tumour proliferation and metastasis. The molecular switch promoting CLIC1 activation remains under investigation. Here, cellular Cl- efflux assays and immunofluorescence microscopy studies have identified intracellular Zn2+ release as the trigger for CLIC1 activation and membrane insertion. Biophysical assays confirmed specific binding to Zn2+, inducing membrane association and enhancing Cl- efflux in a pH-dependent manner. Together, our results identify a two-step mechanism with Zn2+ binding as the molecular switch promoting CLIC1 membrane insertion, followed by pH-mediated activation of Cl- efflux.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cloretos
/
Canais de Cloreto
Idioma:
En
Revista:
J Cell Sci
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Reino Unido