Abstract
TRPC6 is activated by direct exposure to diacylglycerol (DAG) produced by isoforms of the PLC family. Mutations in TRPC6 and PLCε identified in patients with nephrotic syndrome of the kidney link these proteins to structural components of the glomerular slit diaphragm in podocytes. For that reason we investigated, if there is a functional interaction between these two proteins. We were able to coimmunoprecipitate PLCε and TRPC6 in primary murine podocytes. Furthermore, siRNA mediated downregulation of endogenous PLCε in HEK 293 cells evoked a reduction of TRPC6 specific currents. The importance of this mechanism was further emphasized by the fact that murine podocytes showed an angiotensin II‐induced increase in barrier function, which was mimicked by OAG, a membrane permeable DAG‐analogue. Most interestingly, TRPC6‐/‐ podocytes isolated from TRPC6‐deficient mice displayed a markedly decreased barrier function in comparison to wild‐type cells. Similar results were obtained in PLCε‐/‐ podocytes. These data suggest an important role of PLCε in the regulation of TRPC6 activity in glomerular podocytes, and may provide inroads into the understanding of AT1 receptor blocker treatment in nephrotic syndrome.
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