| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Research Abstract |
A specialized intercellular junction between podocytes, known as the slit diaphragm (SD), forms the essential structural framework for glomerular filtration in the kidney. In addition, mounting evidence demonstrates that SD also plays a crucial role as a signaling platform in physiological and pathological states. Nephrin, the major component of SD, is tyrosine phosphorylated by a Src-family tyrosine kinase, Fyn, in developing or injured podocytes. In this study, we performed proteomic analysis searching for proteins binding with phosphorylated Nephrin, and identified several novel interacting protein including phospholipase C-γ1PLC-γ1. Furthermore, phosphorylation of Nephrin is directly involved in Ca^<2+> homeostasis via the recruitment and activation of PLC-γ1. These results strongly suggest that the SD structure is directly linked to Ca^<2+> signaling by PLC-γ1, and demonstrate a novel role of SD as an orchestrator of versatile signaling pathway.
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