The organic anion transporter SLCO2A1 constitutes the core component of the Maxi-Cl channel.
EMBO J
; 36(22): 3309-3324, 2017 11 15.
Article
em En
| MEDLINE
| ID: mdl-29046334
The maxi-anion channels (MACs) are expressed in cells from mammals to amphibians with ~60% exhibiting a phenotype called Maxi-Cl. Maxi-Cl serves as the most efficient pathway for regulated fluxes of inorganic and organic anions including ATP However, its molecular entity has long been elusive. By subjecting proteins isolated from bleb membranes rich in Maxi-Cl activity to LC-MS/MS combined with targeted siRNA screening, CRISPR/Cas9-mediated knockout, and heterologous overexpression, we identified the organic anion transporter SLCO2A1, known as a prostaglandin transporter (PGT), as a key component of Maxi-Cl. Recombinant SLCO2A1 exhibited Maxi-Cl activity in reconstituted proteoliposomes. When SLCO2A1, but not its two disease-causing mutants, was heterologously expressed in cells which lack endogenous SLCO2A1 expression and Maxi-Cl activity, Maxi-Cl currents became activated. The charge-neutralized mutant became weakly cation-selective with exhibiting a smaller single-channel conductance. Slco2a1 silencing in vitro and in vivo, respectively, suppressed the release of ATP from swollen C127 cells and from Langendorff-perfused mouse hearts subjected to ischemia-reperfusion. These findings indicate that SLCO2A1 is an essential core component of the ATP-conductive Maxi-Cl channel.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transportadores de Ânions Orgânicos
/
Canais Iônicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
/
Humans
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Japão