| Project/Area Number |
24500443
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Yokohama City University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
ARITA Kyohei 横浜市立大学, 生命ナノシステム科学研究科, 准教授 (40549648)
YAMASHITA Naoya 横浜市立大学, 医学研究科, 客員講師 (40508793)
HASHIMOTO Hiroshi 静岡県立大学, 薬学部, 教授 (40336590)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 神経回路形成 / 細胞骨格 / アクチン / セマフォリン / Sema3A / CRMP1 / Filamin-A / リン酸化 / Filamin / フィラミン / 線虫 |
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| Outline of Final Research Achievements |
Sema3A, an axon guidance molecule, repels neurite outgrowth. This action accompanies the collapse of actin-cytoskeleton in the neuronal growth cones. We found that CRMP1, an intracellular mediator for Sema3A-signaling, interacts with Filamin-A, an actin binding protein. In C. elegans, Filamin-1 (Filamin-A homologue) is involved in DD/VD motoneuron guidance with UNC-33 (CRMP1 homologue). CRMP1 binds N- and C-termini of Filamin-A and alters its ternary structure. We determined the interaction residues in Filamin-A and CRMP1. Overexpression of the point-mutants of those residues in cultured neurons interferes Sema3A-response. Sema3A induces phosphorylation of CRMP1. A phospho-mimicking mutant of CRMP1 binds Filamin-A with higher affinity than wildtype. The phospho-mimicking CRMP1 interferes the actin cytoskeleton weaved with F-actin and Filamin-A. These results suggest that phosphorylated CRMP1 removes Filamin-A from actin-cytoskeleton in turn to bring the collapse in Sema3A-signaling.
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