2004 Fiscal Year Final Research Report Summary
Identification of novel Wnt signaling molecules.
| Project/Area Number |
15570119
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
KISHIDA Shosei Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (50274064)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Wnt / β-catenin pathway / PCP pathway / Dvl / Rho-kinase / neurite outgrowth / Daple |
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| Research Abstract |
Dvl is a important protein that transmits the Wnt signal to the β-catenin pathway and PCP (Planar Cell Polarity) pathway. Although it is reported that PCP pathway cytoskeleton by activation of Rho-associated kinase and Jun-kinase, the role of Dvl and PCP pathway in mammalian cells remains unclear.
The following observations were obtained in this research.
1.Activation of Rho-associated kinase by Wnt and Dvl in mammalian cells
The expression of Dvl-1,Wnt-1, or Wnt-3a activated Rho-associated kinase in COS cells.
2.Inhibition of neurite outgrowth by Wnt and Dvl
The expression of Dvl-1 in PC12 rat pheochromocytoma cells activated RhoA and induced ring-like actin fiber formation and suppressed NGF-dependent-neurite outgrowth. The expression of Wnt-1 or Dvl-1 in rat PC12 cells suppressed NGF-dependent neurite outgrowth.
The expression of Dvl-1 in N1E-115 mouse neuroblastoma cells also inhibited serum starvation-dependent neurite outgrowth and the co-expression of Rho-binding domain of Rho associated kinase reversed this action of Dvl-1. Dvl-1 mutants that does not activate Rho-associated kinase did not inhibit the neurite out growth of N1E-115 cells.
3.Identification of Daple, a novel Dvl-binding protein.
We identified a novel protein that binds to Dvl and named it Daple. Daple consists of 2009 amino acids. The c-terminal three amino acids were required for the binding to the PDZ domain of Dvl. The expression of Daple inhibited Wnt-3a dependent Tcf-activation in L cells. Daple also inhibited Dvl-induced secondary axis formation in Xenopus embryos.
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