Mastroianni N, De Fusco M, Zollo M, Arrigo G, Zuffardi O, Bettinelli A, Ballabio A, Casari G
Telethon Institute of Genetics and Medicine (Tigem), San Raffaele Biomedical Science Park, Milan, Italy.
Genomics. 1996 Aug 1;35(3):486-93. doi: 10.1006/geno.1996.0388.
Electrolyte homeostasis is maintained by several ion transport systems. Na-(K)-Cl cotransporters promote the electrically silent movement of chloride across the membrane in absorptive and secretory epithelia. Two kidney-specific Na-(K)-Cl cotransporter isoforms are known, so far, according to their sensitivity to specific inhibitors. We have cloned the human cDNA coding for the renal Na-Cl cotransporter selectively inhibited by the thiazide class of diuretic agents. The predicted protein sequence of 1021 amino acids (112 kDa) shows a structure common to the other members of the Na-(K)-Cl cotransporter family: a central region harboring 12 transmembrane domains and the 2 intracellular hydrophilic amino and carboxyl termini. The expression pattern of the human Na-Cl thiazide-sensitive cotransporter (hTSC, HGMW-approved symbol SLC12A3) confirms the kidney specificity. hTSC has been mapped to human chromosome 16q13 by fluorescence in situ hybridization. The cloning and characterization of hTSC now render it possible to study the involvement of this cotransport system in the pathogenesis of tubulopathies such as Gitelman syndrome.
电解质平衡由多种离子转运系统维持。钠 - 钾 - 氯协同转运蛋白促进氯离子在吸收性和分泌性上皮细胞中跨膜的电中性移动。根据对特定抑制剂的敏感性，目前已知两种肾脏特异性的钠 - 钾 - 氯协同转运蛋白亚型。我们已经克隆了编码受噻嗪类利尿剂选择性抑制的肾脏钠 - 氯协同转运蛋白的人类cDNA。预测的1021个氨基酸（112 kDa）的蛋白质序列显示出钠 - 钾 - 氯协同转运蛋白家族其他成员共有的结构：一个包含12个跨膜结构域以及两个细胞内亲水性氨基和羧基末端的中心区域。人类钠 - 氯噻嗪敏感协同转运蛋白（hTSC，HGMW批准符号SLC12A3）的表达模式证实了其肾脏特异性。通过荧光原位杂交，hTSC已被定位到人类染色体16q13。hTSC的克隆和特性分析现在使得研究这种协同转运系统在诸如吉特曼综合征等肾小管疾病发病机制中的作用成为可能。
