Huber Tobias B, Schermer Bernhard, Benzing Thomas
Renal Division, University Hospital Freiburg, Freiburg, Germany.
Nephron Exp Nephrol. 2007;106(2):e27-31. doi: 10.1159/000101789. Epub 2007 Jun 6.
The slit diaphragm is part of a three-layered glomerular filter that prevents most proteins from entering the urinary space. As a highly specialized cell-cell contact the slit diaphragm has recently been appreciated as a signaling platform that regulates podocyte cell survival, polarity, endocytosis and cytoskeletal organization. Mutations in genes encoding slit diaphragm proteins contribute to human hereditary glomerular diseases. Recently, it was discovered that transient receptor potential ion channel TRPC6 mutations cause familial glomerular disease. TRPC6 localizes to the slit diaphragm unexpectedly adding an ion channel to the list of signaling molecules functioning at this complex structure. Recent findings highlight a potential role for TRPC6 at the filtration barrier. TRPC6 has been identified as a sensor of mechanically and osmotically induced membrane stretch. In the context of the slit diaphragm signaling network, TRPC6 is clustered and regulated by a podocin-lipid complex that might translate mechanical tension to ion channel action. This review will summarize the most recent findings on protein-lipid supercomplexes at the slit diaphragm and discuss a potential novel function of the slit diaphragm as a mechanosensor.
裂孔隔膜是三层肾小球滤过屏障的一部分，可阻止大多数蛋白质进入尿液空间。作为一种高度特化的细胞间接触结构，裂孔隔膜最近被认为是一个信号平台，可调节足细胞的细胞存活、极性、内吞作用和细胞骨架组织。编码裂孔隔膜蛋白的基因突变会导致人类遗传性肾小球疾病。最近发现，瞬时受体电位离子通道TRPC6突变会引发家族性肾小球疾病。TRPC6定位于裂孔隔膜，这意外地为在这个复杂结构中发挥作用的信号分子列表增添了一种离子通道。最近的研究结果突出了TRPC6在滤过屏障中的潜在作用。TRPC6已被确定为机械和渗透诱导的膜拉伸的传感器。在裂孔隔膜信号网络的背景下，TRPC6由一种足动蛋白 - 脂质复合物聚集和调节，该复合物可能将机械张力转化为离子通道作用。本综述将总结裂孔隔膜处蛋白质 - 脂质超复合物的最新研究结果，并讨论裂孔隔膜作为机械传感器的潜在新功能。
