The Pendred syndrome gene encodes a chloride-iodide transport protein
The Pendred syndrome gene encodes a chloride-iodide transport protein
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DOI：
10.1038/7783
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发表时间：
1999-04-01
期刊：
影响因子：
30.8
通讯作者：
Karniski, LP
中科院分区：
文献类型：
--
作者：
Scott, DA;Wang, R;Karniski, LP
Pendred综合征是综合征性耳聋的最常见形式，其特征为先天性感音神经性听力损失和甲状腺肿（1-3）。这种疾病被定位于7号染色体，随后通过定位克隆鉴定了引起Pendred综合征（PDS）的基因（4-6）。PDS编码一种假定的跨膜蛋白，命名为pendrin。Pendrin与包括大鼠硫酸盐阴离子转运蛋白在内的硫酸盐转运蛋白家族密切相关（7）（由Sat-1编码; 29%氨基酸序列同一性），人骨发育不良硫酸盐转运蛋白（8）（由DTD编码; 32%）和人硫酸盐转运蛋白“在腺瘤中下调”（9，10）基于这种同源性和存在包含其推定的第二跨膜结构域的略微修饰的硫酸盐转运蛋白特征序列（6-9），已经提出pendrin作为硫酸盐转运蛋白起作用。我们无法检测到硫酸盐运输的证据pendrin在非洲爪蟾卵母细胞中的PDS cRNA的显微注射或在Sf 9细胞感染后的PDS重组杆状病毒的表达。碘和氯的运输率显着增加后，在两个细胞系统中的pendrin的表达。我们的研究结果表明，pendrin作为氯离子和碘离子的转运蛋白，但不是硫酸盐，并可能提供洞察甲状腺生理和Pendred综合征的病理生理。
Pendred syndrome is the most common form of syndromic deafness and characterized by congenital sensorineural hearing loss and goitre(1-3). This disorder was mapped to chromosome 7 and the gene causing Pendred syndrome (PDS) was subsequently identified by positional cloning(4-6). PDS encodes a putative transmembrane protein designated pendrin. Pendrin is closely related to a family of sulfate transport proteins that includes the rat sulfate-anion transporter(7) (encoded by Sat-1; 29% amino acid sequence identity), the human diastrophic dysplasia sulfate transporter(8) (encoded by DTD; 32%) and the human sulfate transporter 'downregulated in adenoma'(9,10) (encoded by DRA; 45%), On the basis of this homology and the presence of a slightly modified sulfate-transporter signature sequence comprising its putative second transmembrane domain(6-9), pendrin has been proposed to function as a sulfate transporter. We were unable to detect evidence of sulfate transport following the expression of pendrin in Xenopus laevis oocytes by microinjection of PDS cRNA or in Sf9 cells following infection with PDS-recombinant baculovirus. The rates of transport for iodide and chloride were significantly increased following the expression of pendrin in both cell systems. Our results demonstrate that pendrin functions as a transporter of chloride and iodide, but not sulfate, and may provide insight into thyroid physiology and the pathophysiology of Pendred syndrome.