Your browser doesn't support javascript.
loading
The organic anion transporter SLCO2A1 constitutes the core component of the Maxi-Cl channel.
Sabirov, Ravshan Z; Merzlyak, Petr G; Okada, Toshiaki; Islam, Md Rafiqul; Uramoto, Hiromi; Mori, Tomoko; Makino, Yumiko; Matsuura, Hiroshi; Xie, Yu; Okada, Yasunobu.
Afiliação
  • Sabirov RZ; International Collaborative Research Project, National Institute for Physiological Sciences, Okazaki, Japan.
  • Merzlyak PG; Laboratory of Molecular Physiology, Institute of Bioorganic Chemistry, Uzbekistan Academy of Sciences, Tashkent, Uzbekistan.
  • Okada T; International Collaborative Research Project, National Institute for Physiological Sciences, Okazaki, Japan.
  • Islam MR; Laboratory of Molecular Physiology, Institute of Bioorganic Chemistry, Uzbekistan Academy of Sciences, Tashkent, Uzbekistan.
  • Uramoto H; International Collaborative Research Project, National Institute for Physiological Sciences, Okazaki, Japan.
  • Mori T; Division of Cell Signaling, National Institute for Physiological Sciences, Okazaki, Japan.
  • Makino Y; International Collaborative Research Project, National Institute for Physiological Sciences, Okazaki, Japan.
  • Matsuura H; Department of Health and Nutrition, Jin-ai University, Echizen, Japan.
  • Xie Y; Core Research Facilities, National Institute for Basic Biology, Okazaki, Japan.
  • Okada Y; Core Research Facilities, National Institute for Basic Biology, Okazaki, Japan.
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.
Assuntos
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 / Female / Humans Idioma: En Revista: EMBO J Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Japão

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 / Female / Humans Idioma: En Revista: EMBO J Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Japão