TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function
TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function
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DOI：
10.1038/ng1592
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发表时间：
2005-07-01
期刊：
影响因子：
30.8
通讯作者：
Pollak, MR
中科院分区：
文献类型：
--
作者：
Reiser, J;Polu, KR;Pollak, MR
进行性肾衰竭是一组在遗传和临床上具有异质性的疾病。足细胞足突以及介于其间的肾小球裂孔隔膜是肾脏渗透屏障的关键组成部分。编码足细胞结构蛋白的基因发生突变会导致蛋白尿的产生，进而引起进行性肾衰竭和局灶节段性肾小球硬化。在此，我们发现经典瞬时受体电位6（TRPC6）离子通道在足细胞中表达，并且是肾小球裂孔隔膜的一个组成部分。我们确定了5个常染色体显性局灶节段性肾小球硬化的家系，其疾病与11号染色体上的TRPC6基因突变相关联。其中两个TRPC6突变体的电流幅度增加。这些数据表明，裂孔隔膜处的TRPC6通道活性对于足细胞结构和功能的正常调节至关重要。
Progressive kidney failure is a genetically and clinically heterogeneous group of disorders. Podocyte foot processes and the interposed glomerular slit diaphragm are essential components of the permeability barrier in the kidney. Mutations in genes encoding structural proteins of the podocyte lead to the development of proteinuria, resulting in progressive kidney failure and focal segmental glomerulosclerosis. Here, we show that the canonical transient receptor potential 6 ( TRPC6) ion channel is expressed in podocytes and is a component of the glomerular slit diaphragm. We identified five families with autosomal dominant focal segmental glomerulosclerosis in which disease segregated with mutations in the gene TRPC6 on chromosome 11q. Two of the TRPC6 mutants had increased current amplitudes. These data show that TRPC6 channel activity at the slit diaphragm is essential for proper regulation of podocyte structure and function.