Project/Area Number |
18500273
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Nerve anatomy/Neuropathology
|
Research Institution | National Institute of Advanced Industrial Science and Technology |
Principal Investigator |
OCHIISHI Tomoyo National Institute of Advanced Industrial Science and Technology, Neuroscience Research Institute, senior researcher (30356729)
|
Project Period (FY) |
2006 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥4,110,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
Keywords | Neuroscience / Brain・Neuron / Protein / Cell・Tissue / Signa transduction / 蛋白質 |
Research Abstract |
δ-catenin is a neuronal protein, which has ten Armadillo repeats and binds to the juxta-membrane segment of the classical cadherins. Members of this family can exert effects on cell morphology. When delta-catenin was transfected into young cultured rat hippocampal neurons, the number of filopodia increased ; however, this effect was minimal in mature neurons. Delta-catenin binds to several PDZ domain containing post-synaptic proteins such as S-SCAM, Erbin and PSD95. It associates with the second PDZ domain of PSD-95 and this association is regulated by Src family tyrosine phosphorylation of delta-catenin. Stimulation of group 1 metabotropic glutamate receptors with the selective agonist(S) -3, 5-dihydroxyphenylglycine(DHPG) induces tyrosine phosphorylation of delta-catenin, dissociation of delta-catenin from PSD-95, and the emergence of dendritic filopodia in mature hippocampal neurons. The ability of delta-catenin to induce filopodia when dissociated from its PDZ domain-containing targets was demonstrated with a delta-catenin carboxy terminal truncation that removed only the PDZ binding motif, a competitive displacement of endogenous delta-catenin by a peptide corresponding to the PDZ binding motif of delta-catenin, and selective displacement of endogenous delta-catenin by specific PDZ domain targets of delta-catenin in mature neurons. These findings suggest that the binding of delta-catenin to its PDZ targets is activity regulated and can trigger or inhibit filopodial elaboration.
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