Identification and properties of a novel variant of NBC4 (Na+/HCO3- co-transporter 4) that is predominantly expressed in the choroid plexus

Identification and properties of a novel variant of NBC4 (Na+/HCO3- co-transporter 4) that is predominantly expressed in the choroid plexus
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DOI:
10.1042/bj20121515
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发表时间:
2013-02-15
影响因子:
4.1
通讯作者:
Hirose, Shigehisa
Hirose, Shigehisa
中科院分区:
生物学3区
文献类型:
--
作者:
Fukuda, Hidekazu;Hirata, Taku;Hirose, Shigehisa

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脉络膜丛上皮细胞顶侧分泌HCO3-是脑脊液形成的重要步骤。已观察到具有高HCO3-渗透性的阴离子传导,并认为这是HCO3-通过顶膜运输的主要途径。近年来,人们发现NBC家族的致电性成员NBC (Na+/HCO3-共转运体)4在脉络膜丛中表达。我们发现,NBC4的一种新变体[NBC4g/51c4a5(溶质载体家族4,碳酸氢钠共转运体,成员5)]几乎只在大鼠脉络膜丛上皮的顶膜中高水平表达。RNA干扰介导的敲除功能证明NBC4g是HCO3-在脉络丛上皮顶膜运输中的主要参与者;结合最近在脉络膜丛上皮细胞中电致NBC的化学计量比为3:1的观察结果,本研究的结果表明,NBC4g介导HCO3-的外排,并有助于脑脊液的产生。
Secretion of HCO3- at the apical side of the epithelial cells of the choroid plexus is an essential step in the formation of cerebrospinal fluid. Anion conductance with a high degree of HCO3- permeability has been observed and suggested to be the major pathway for HCO3- transport across the apical membrane. Recently, it was found that NBC (Na+/HCO3- co-transporter) 4, an electrogenic member of the NBC family, was expressed in the choroid plexus. We found that a novel variant of the NBC4 [NBC4g/51c4a5 (solute carrier family 4, sodium bicarbonate cotransporter, member 5)] is almost exclusively expressed in the apical membrane of rat choroid plexus epithelium at exceptionally high levels. RNA interference-mediated knockdown allowed the functional demonstration that NBC4g is the major player in the HCO3- transport across the apical membrane of the choroid plexus epithelium; When combined with a recent observation that in choroid plexus epithelial cells electrogenic NBC operates with a stoichiometry of 3:1, the results of the present study suggest that NBC4g mediates the efflux of HCO3- and contributes to cerebrospinal fluid production.