2009 Fiscal Year Final Research Report
糸球体上皮細胞シグナル伝達系のプロテオミクス解析による蛋白尿発症機序の解明
| Project/Area Number |
20790719
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HARITA Yutaka The University of Tokyo, 生命ナノシステム科学研究科, 特任助教 (10451866)
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| Project Period (FY) |
2008 – 2009
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| Keywords | 小児腎 / 泌尿器学 |
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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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[Journal Article] Patients with Epstein-Fechtner syndromes owing to MYH9 R702 mutations develop progressive proteinuric renal disease.
Author(s)
Sekine T, Konno M, Sasaki S, Moritani S, Miura T, Wong WS, Nishio H, Nishiguchi T, Ohuchi MY, Tsuchiya S, Matsuyama T, Kanegane H, Ida K, Miura K, Harita Y, Hattori M, Horita S, Igarashi T, Saito H, Kunishima S
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Journal Title
Kidney International (in press)
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[Journal Article] Glomerular proteins related to slit diaphragm and matrix adhesion in the foot processes are highly tyrosine phosphorylated in the normal rat kidney.
Author(s)
Zhang Y, Yoshida Y, Nameta M, Xu B, Taguchi I, Ikeda T, Fujinaka H, Mohamed SM, Tsukaguchi H, Harita Y, Yaoita E, Yamamoto T
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Journal Title
Nephrol Dial Transplant (in press)
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