Molecular mechanism of the synapse formation by neuronal activity
| Project/Area Number |
15300130
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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 Organization for Medical Research |
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Principal Investigator |
YAMAGATA Kanato Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Director, 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) |
SUGIURA Hiroko Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Research Staff, 研究員 (40162870)
TANAKA Hidekazu Osaka University, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 助手 (70273638)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥16,700,000 (Direct Cost: ¥16,700,000)
Fiscal Year 2005: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2004: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2003: ¥6,900,000 (Direct Cost: ¥6,900,000)
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| Keywords | neural activity / synapse / plasticity / cadherin / endocytosis / Arcadlin / FRET / N-cadherin / TAO2 / p38 MAP kinase / splicing / スライス培養 / 遺伝子導入 / 細胞接着分子 / プロトカドヘリン / リン酸化 |
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| Research Abstract |
How does neural activity remodel synapses? We previously reported a novel protocadherin designated Arcadlin was strongly induced in the brain by neural activity. Here, we show that this protocadherin Arcadlin is involved in the remodeling of spine membrane by regulating N-cadherin that that play a crucial role in synapse formation. Arcadlin synthesis is induced by neural stimulation and it is transported to the synaptic membrane, where it binds to N-cadherin. Overexpressed Arcadlin protocadherin drives N-cadherin into endosomes and suppresses the generation of dendritic filopodia and spines. Consistently, neurons from Arcadlin/PAPC homozygous mutant mice form a larger number of synaptic puncta than wild-type neurons. During our investigations into the intracellular signaling mechanism that activates the endocytosis of N-cadherin with Arcadlin, we identified a novel splice form of TAO2 kinase (TAO2β) as an intracellular binding partner of the Arcadlin protocadherin. Homophilic interacti
… More
on of Arcadlin on cell surface activates p38 MAPK through the activation of TAO2β. In turn, active p38 MAPK feeds back on TAO2β, phosphorylating its carboxy-terminal domain at a specific Serine. This triggers the co-endocytosis of N-cadherin/Arcadlin/TAO2β complex in HEK293T cells and hippocampal neurons. We propose that endocytosis regulated by this novel signal transduction pathway involving a protocadherin, a MAPKKK that binds to its intracellular domain, a MAPK and a classical cadherin modulates the adhesiveness and morphology of spine membranes, resulting in changes in synaptic strength induced by neural activity. In the future, it will be interesting to investigate behavior and memory in mice mutant for the Arcadlin protocadherin. The adhesive apparatus of synaptic spine membranes in the peri-synaptic region can now be recognized as a focal point of vigorous remodeling. Involvement of p38 MAPK-induced endocytosis may provide a possible relationship between the modulation of adhesive machinery and the insertion/removal of neurotransmitter receptors. Less
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Report
(4 results)
Research Products
(32 results)
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[Journal Article] Augmentation of allergic inflammation in the airways of cyclooxygenase-2-deficient mice.2005
Author(s)
Nakata, J., Kondo, M., Tamaoki, J., Takemiya, T., Nohara, M., Yamagata, K., Nagai, A.
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Journal Title
Respirology. 10(2)
Pages: 149-156
Description
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[Journal Article] Inhibitory Role of Endophilin 3 in Receptor-mediated Endocytosis.2004
Author(s)
Sugiura, H., Iwata, K., Matsuoka, M., Hayashi, H., Takemiya, T., Yasuda, S., Ichikawa, M., Yamauchi, T., Mehlen, P., Haga, T., Yamagata, K.
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Journal Title
J Biol Chem 279
Pages: 23343-23348
Description
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[Journal Article] Amelioration of hippocampal neuronal damage after transient forebrain ischemia in cyclooxygenase-2-deficient mice.2004
Author(s)
Sasaki, T., Kitagawa, K., Yamagata, K., Takemiya, T., Tanaka, S., Omura-Matsuoka, E., Sugiura, S., Matsumoto, M., Hori, M.
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Journal Title
J Cereb Blood Flow Metab. 24(1)
Pages: 107-113
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[Journal Article] Inducible brain COX-2 facilitates the recurrence of hippocampal seizures in mouse rapid kindling.2003
Author(s)
Takemiya, T., Suzuki, K., Sugiura, H., Yasuda, S., Yamagata, K., Kawakami, Y., Maru, E.
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Journal Title
Prostaglandins Other Lipid Mediat 71
Pages: 205-216
Description
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[Journal Article] Rapid induction of Arc is observed in the granule cell dendrites in the accessory olfactory bulb after mating.2003
Author(s)
Matsuoka, M., Yoshida-Matsuoka, J., Yamagata, K., Sugiura, H., Ichikawa, M., Norita, M.
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Journal Title
Brain Research 975
Pages: 189-195
Description
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[Journal Article] Interaction of Arc with CaM kinase II and stimulation of neurito extension by Arc in neuroblastoma cells expressing CaM kinase II.2003
Author(s)
Donai, H., Sugiura, H., Ara, D., Yoshimura, Y., Yamagata, K., Yamauchi, T.
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Journal Title
Neurosci Res 47
Pages: 399-408
Description
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