A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis
A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis
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DOI：
10.1126/science.1106215
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发表时间：
2005-06-17
期刊：
影响因子：
56.9
通讯作者：
Rosenberg, PB
中科院分区：
文献类型：
--
作者：
Winn, MP;Conlon, PJ;Rosenberg, PB
局灶节段性肾小球硬化症（FSGS）是一种病因不明的肾脏疾病，多达20%的透析患者被诊断患有此病。在此我们表明，一个患有遗传性FSGS的大家族在11号染色体q臂的TRPC6基因上存在一个错义突变，该基因编码离子通道蛋白瞬时受体电位阳离子通道6（TRPC6）。在该蛋白高度保守区域的第112位脯氨酸被谷氨酰胺取代，增强了TRPC6对血管紧张素II等激动剂的介导的钙信号，并似乎改变了TRPC6蛋白的细胞内分布。先前的研究强调了细胞骨架和结构蛋白在蛋白尿性肾脏疾病中的重要性。我们的研究结果提示了肾小球疾病发病机制的另一种机制。
Focal and segmental glomerulosclerosis (FSGS) is a kidney disorder of unknown etiology, and up to 20% of patients on dialysis have been diagnosed with it. Here we show that a large family with hereditary FSGS carries a missense mutation in the TRPC6 gene on chromosome 11q, encoding the ion-channel protein transient receptor potential cation channel 6 (TRPC6). The proline-to-glutamine substitution at position 112, which occurs in a highly conserved region of the protein, enhances TRPC6-mediated calcium signals in response to agonists such as angiotensin II and appears to alter the intracellular distribution of TRPC6 protein. Previous work has emphasized the importance of cytosketetal and structural proteins in proteinuric kidney diseases. Our findings suggest an alternative mechanism for the pathogenesis of glomerular disease.