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人类五个新的假定阴离子转运蛋白基因的定位以及胰腺阴离子交换蛋白候选基因SLC26A6的特性分析

Mapping of five new putative anion transporter genes in human and characterization of SLC26A6, a candidate gene for pancreatic anion exchanger.

作者信息

Lohi H, Kujala M, Kerkelä E, Saarialho-Kere U, Kestilä M, Kere J

机构信息

Department of Medical Genetics, University of Helsinki, Helsinki, Finland.

出版信息

Genomics. 2000 Nov 15;70(1):102-12. doi: 10.1006/geno.2000.6355.

Abstract

A second distinct family of anion transporters, in addition to the classical SLC4 (or AE) family, has recently been delineated. Members of the SLC26 family are structurally well conserved and can mediate the electroneutral exchange of Cl(-) for HCO(-)(3) across the plasma membrane of mammalian cells like members of the SLC4 family. Three human transporter proteins have been functionally characterized: SLC26A2 (DTDST), SLC26A3 (CLD or DRA), and SLC26A4 (PDS) can transport with different specificities the chloride, iodine, bicarbonate, oxalate, and hydroxyl anions, whereas SLC26A5 (prestin) was suggested to act as the motor protein of the cochlear outer hair cell. We report the expansion of the SLC26 family with five new members in chromosomes 3, 6, 8, 12, and 17 and mapping of SLC26A1 to 4p16.3. We have characterized one of them, SLC26A6, in more detail. It maps to chromosome 3p21.3, encodes a predicted 738-amino-acid transmembrane protein, and is most abundantly expressed in the kidney and pancreas. Pancreatic ductal cell lines Capan-1 and Capan-2 express SLC26A6, and immunohistochemistry localizes SLC26A6 protein to the apical surface of pancreatic ductal cells, suggesting it as a candidate for a luminal anion exchanger. The functional characterization of the novel members of this tissue-specific gene family may provide new insights into anion transport physiology in different parts of the body.

摘要

除了经典的SLC4(或AE)家族外,最近还发现了第二个不同的阴离子转运蛋白家族。SLC26家族成员在结构上高度保守,并且像SLC4家族成员一样,能够介导哺乳动物细胞质膜上Cl⁻与HCO₃⁻的电中性交换。三种人类转运蛋白已得到功能鉴定:SLC26A2(DTDST)、SLC26A3(CLD或DRA)和SLC26A4(PDS)能够以不同的特异性转运氯离子、碘离子、碳酸氢根离子、草酸根离子和氢氧根离子,而SLC26A5(prestin)被认为是耳蜗外毛细胞的运动蛋白。我们报告了SLC26家族在3号、6号、8号、12号和17号染色体上新增了五个成员,并将SLC26A1定位到4p16.3。我们对其中一个成员SLC26A6进行了更详细的表征。它定位于3号染色体p21.3,编码一个预测的由738个氨基酸组成的跨膜蛋白,在肾脏和胰腺中表达最为丰富。胰腺导管细胞系Capan-1和Capan-2表达SLC26A6,免疫组织化学将SLC26A6蛋白定位到胰腺导管细胞的顶端表面,表明它是管腔阴离子交换体的一个候选蛋白。对这个组织特异性基因家族新成员的功能表征可能会为身体不同部位的阴离子转运生理学提供新的见解。

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