Cation-coupled bicarbonate transporters.
Cation-coupled bicarbonate transporters.
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DOI：
10.1002/cphy.c130005
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发表时间：
2014-10
影响因子：
5.8
通讯作者：
Lee S
中科院分区：
文献类型：
--
作者：
Aalkjaer C;Boedtkjer E;Choi I;Lee S
阳离子偶联的HCO3−转运最早是在20世纪70年代中期被发现的，当时开创性的研究表明，细胞中的酸被CO_2/HCO_3−刺激并与Na+和Cl-−的运动有关。第一个Na+偶联的碳酸氢盐转运蛋白(NCBT)是在20世纪90年代末表达克隆的。目前在SLC4家族中有5个哺乳动物NCBT：电源性Na，HCO3-共转运体NBCe1和NBCe2(SLC4A4和SLC4A5基因产物)；电子中性型Na，HCO3-共转运体NBCn1(SLC4A7基因产物)；Na+驱动的Na，HCO3-交换器NDCBE(SLC4A8基因产物)；以及NBCn2/NCBE(SLC4A10基因产物)，它被鉴定为电子中性物Na，HCO3-共转运体或Na+驱动的ClHCO3-交换器。尽管SLC4家族的NCBT在氨基酸序列和预测结构上具有相似性，但它们在离子依赖性、转运功能、药理性质以及与其他蛋白质的相互作用方面表现出明显的差异。在上皮细胞中，NCBT参与了酸碱等效物的跨细胞移动和细胞内pH的控制。在非上皮性组织中，NCBT有助于调节细胞内的pH；因此，它们对包括神经元放电、感觉神经元发育、心脏功能和血管张力调节在内的各种组织功能至关重要。NCBT的功能和表达水平通常对细胞内和系统的pH敏感。动物模型揭示了转运蛋白在代谢性酸中毒、高血压、视力缺陷和癫痫发作等疾病状态下的病理生理作用。目前正在进行研究，以了解SLC4成员基因多态的生理后果，这些基因多态与癌症、高血压和药物成瘾有关。在这里，我们描述了目前关于哺乳动物阳离子偶联HCO3SLC4家族−转运蛋白的功能、结构和调控的知识。
Cation-coupled HCO3− transport was initially identified in the mid-1970s when pioneering studies showed that acid extrusion from cells is stimulated by CO2/HCO3− and associated with Na+ and Cl− movement. The first Na+-coupled bicarbonate transporter (NCBT) was expression-cloned in the late 1990s. There are currently five mammalian NCBTs in the SLC4-family: the electrogenic Na,HCO3-cotransporters NBCe1 and NBCe2 (SLC4A4 and SLC4A5 gene products); the electroneutral Na,HCO3-cotransporter NBCn1 (SLC4A7 gene product); the Na+-driven Cl,HCO3-exchanger NDCBE (SLC4A8 gene product); and NBCn2/NCBE (SLC4A10 gene product), which has been characterized as an electroneutral Na,HCO3-cotransporter or a Na+-driven Cl,HCO3-exchanger. Despite the similarity in amino acid sequence and predicted structure among the NCBTs of the SLC4-family, they exhibit distinct differences in ion dependency, transport function, pharmacological properties, and interactions with other proteins. In epithelia, NCBTs are involved in transcellular movement of acid-base equivalents and intracellular pH control. In nonepithelial tissues, NCBTs contribute to intracellular pH regulation; and hence, they are crucial for diverse tissue functions including neuronal discharge, sensory neuron development, performance of the heart, and vascular tone regulation. The function and expression levels of the NCBTs are generally sensitive to intracellular and systemic pH. Animal models have revealed pathophysiological roles of the transporters in disease states including metabolic acidosis, hypertension, visual defects, and epileptic seizures. Studies are being conducted to understand the physiological consequences of genetic polymorphisms in the SLC4-members, which are associated with cancer, hypertension, and drug addiction. Here, we describe the current knowledge regarding the function, structure, and regulation of the mammalian cation-coupled HCO3− transporters of the SLC4-family.
用vallyomycin或gramicidin处理的人红细胞中DIDS不敏感的氯化物电导的电辐射，屏障和门控分析。
影响因子：
3.8
作者：
Freedman, J C;Novak, T S
通讯作者：
Novak, T S