| Project/Area Number |
13480261
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Tokyo Metropolitan Institute for Neuroscience |
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Principal Investigator |
YAMAGATA Kanato Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Staff Scientist, 東京都神経科学総合研究所, 副参事研究員 (20263262)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Hidekazu Osaka University Graduate School of Medicine, Department of Pharmacology, Assistant Professor, 大学院・医学系研究科, 助手 (70273638)
SUGIURA Hiroko Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Staff Scientist, 東京都神経科学総合研究所, 研究員 (40162870)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥15,100,000 (Direct Cost: ¥15,100,000)
Fiscal Year 2002: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2001: ¥9,300,000 (Direct Cost: ¥9,300,000)
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| Keywords | neural activity / cell adhesion molecule / cadherin / 神経接着分子 / MAP kinase |
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| Research Abstract |
We investigated the role of activity-regulated adhesion molecule arcadlin. Arcadlin is synthesized in neurons and carried to synapses and may be involved in synaptic reorganization stimulated by synaptic activity. Here, we analyzed the interaction of TAO2 with the cytoplasmic region of Arcadlin. Homophilic binding of extracellular (EC) domains of arcadlin activated TAO2 and its down-stream kinases, MKK3 and p38 MAP kinase. The homophilic interaction also induced the internalization of arcadlin itself. This internalization was completely blocked by the co-expression of dominant-negative dynamin, indicating that arcadlin was internalized by clathrin-mediated endocytosis. The absence of MKK3 and p38 MARK resulted in a loss of arcadlin endocytosis. Moreover, p38 MARK inhibitor SB203580 also inhibited the endocytosis of arcadlin. These results suggest that TAO2, stimulated by homophilic binding of arcadlin EC domains, activates p38 MAP kinase pathway and induces the endocytosis of arcadlin. Thus, neural activity may play a role in changing the strength of synaptic connections by regulating the number of cell adhesion molecules on the surface of synaptic membranes.
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