| Project/Area Number |
17082006
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Yokohama City University |
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Principal Investigator |
GOSHIMA Yoshio Yokohama City University, 医学研究科, 教授 (00153750)
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| Co-Investigator(Kenkyū-buntansha) |
OOSHIMA Toshio 早稲田大学, 理工学術院, 教授 (20311334)
中村 史雄 横浜市立大学, 医学研究科, 准教授 (10262023)
内田 穣 横浜市立大学, 医学研究科, 特任教員
鈴木 厚 横浜市立大学, 医学研究科, 準教授 (00264606)
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| Project Period (FY) |
2005 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥101,700,000 (Direct Cost: ¥101,700,000)
Fiscal Year 2009: ¥17,400,000 (Direct Cost: ¥17,400,000)
Fiscal Year 2008: ¥17,000,000 (Direct Cost: ¥17,000,000)
Fiscal Year 2007: ¥17,200,000 (Direct Cost: ¥17,200,000)
Fiscal Year 2006: ¥19,000,000 (Direct Cost: ¥19,000,000)
Fiscal Year 2005: ¥31,100,000 (Direct Cost: ¥31,100,000)
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| Keywords | CRMP / セマフォリン / プレキシン / 神経ガイダンス / 組織構築 / 軸索ガイダンス分子 / Sema3A / Netrin / UNC-51 / axonal transport / Vab-8 / Slit / 細胞移動 / 皮質 / 軸索ガイダンス / ノックアウトマウス |
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| Research Abstract |
In developing brain, axon and dendritic guidance are regulated by repulsive and attractive axon guidance molecules such as semaphorin3A (Sema3A) and netrin. Collpapsin response mediator protein (CRMP) has originally been identified as an intracellular protein that mediates Sema3A. We found that Sema3A elicits axoplasmic transport that may be involved in regulating the localization of AMPA type glutamate receptors in hippocampal neurons. To elucidate in vivo role of CRMPs, we generated several crmp1 and other crmp family gene-deficient mice and performed phenotypic analysis of these mice. For instance, in crmp1-deficient mice, the cell migration of cortical neurons at early embryonic stages is retarded. CRMP1 is colocalized with disabled-1 (Dab1), an adaptor protein in Reln signaling. In the Relnrl/rl cortex, CRMP1 and Dab1 are expressed at a higher level, yet tyrosine phosphorylated at a lower level. Loss of crmp1 in a dab1 heterozygous background lead to the disruption of hippocampal lamination, a Reeler-like phenotype. CRMP1 is also involved in Sema3A-induced localization of AMPA receptors and spine development in the cerebral cortex. In the cultured cortical neurons from crmp1 mice, Sema3A increases the density of clusters of synapsin I and postsynaptic density-95, but this increase is markedly attenuated in crmp1-deficient mice. In our study of C. elegans, we identified several mutant alleles which show aberrant localization of netrin/UNC-6 and axon guidance defects. We therefore conclude that the regulation of the glutamate receptor and the axon guidance molecule localization may play an important role in a wide variety of developmental processes from cell migration to neural network formation.
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