Identification of molecules responsible for the development of nephritic syndrome

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In the present study, at first, we identified the phosphorylation of npeh1, which consists of slit membrane of glimerular podocyte. In addition, we determined the tyrosine residues, which are phosphorylated in protamine sulfate and PAN nephrosis model animals.In the second year, we performed the analysis of signal transduction in podocyte after tyrosine phosphorylation of neph1 and nephrin. The following two points are critical.1. Neph1, PLCγ and TRPC constitute molecular complex in podocyte.2. Function of TRPC6 is regulated by phosphorylatiion of nephrin.TRPC6 is a molecule, whose genetic mutations induce human hereditary nephritic syndrome. The fact that neph1, PLCγ and TRPC constitute molecular complex in podocyte strongly suggest that the phosphorylation of neph1 is associated with the development of nephritic syndrome.Furthermore, regulation of TRPC6 channel by nphrin phosphorylation also suggests its critical role in nephrosis.