| Project/Area Number |
06558106
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 試験 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Keio University |
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Principal Investigator |
UYEMURA Keiichi Dept of Physiol, Keio univ School of Med, Professor, 医学部, 教授 (90049792)
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| Co-Investigator(Kenkyū-buntansha) |
SUGAWA Makoto Chugai Pharmaceutical Co, LTD,Lab Chief, 研究主査
ASOU Hiroaki Dept of Neuro-Cell Biol, Tokyo Met Inst of Gerontol Head, 部門長 (30104160)
TAKEDA Yasuo Dept of Physiol, Keio univ School of Med, Instructor, 医学部, 助手 (60245462)
YAZAKI Takahito Dept of Physiol, Keio univ School of Med, Assistant Professor, 医学部, 専任講師 (80200484)
OKAMOTO Hitoshi Dept of Physiol, Keio univ School of Med, Assistant Professor, 医学部, 専任講師 (40183769)
村上 健一 慶應義塾大学, 医学部, 助手 (30239488)
松本 二郎 慶應義塾大学, 法学部, 教授 (80051241)
中尾 純治 慶応義塾大学, 医学部, 助手 (80255570)
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥9,900,000 (Direct Cost: ¥9,900,000)
Fiscal Year 1996: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1995: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1994: ¥5,100,000 (Direct Cost: ¥5,100,000)
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| Keywords | Neural regeneration / Cell adhesion molecule / Immunoglobulin superfamily / Neurite outgrowth / Neuronal migration / Schwann cells / Graft / Astrocyte / 細胞接着蛋白 / 細胞移動促進 / 変異ヘルペスウイルスベクター / 遺伝的水頭症 / GGF / L1 / PO / 脊髄損傷 / 神経線維の束化 / P0 / 神経細胞移動促進作用 / 神経再生機能 |
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| Research Abstract |
L1 protein is a neural cell adhesion membrane of immunoglobulin superfamily. Recent studies revealed that L1 gene mutation cause impairment of neural morphogenesis and mental retardation. We have reported the deduce amino acid sequences of rat and human L1 and the physiological function of L1, such as promotion of neurite outgrowth and neuronal migration.
1. In addition to full-length L1, we identified the alternatively spliced variant lacking both five and four amino acids in the extracellular and the cytoplasmic domains, respectively. This L1 variant was expressed exclusively in non-neuronal cells, such as Schwann cells. The cells expressing L1 with the short cytoplasmic domain showed lower cell migration activity, suggesting the importance of phosphorylation sites in the sequence for migrating activity.
2. We identified new cell adhesion protein "neurin1" of 68 kD,which expressed in neuronal membrane including growth cone and promoted neurite extension and cell migration as L1 protein. However, neurin1 is different from L1 judging from their molecular weight, amino-terminal sequence and distribution.
3. L cells of fibroblast origin, which was transfected L1cDNA and expressed L1 protein, were grafted to a lesion of rat spinal cord after hemisecion. The graft promoted regeneration of the axonsremarkably in the injured cord 2 weeks after grafting. The results suggest L1 can provide an environment suitable for regeneration of the axons in the injured nervous system.
4. We transfected L1cDNA in primary astrocytes using defective herpes simplex virus vector. The astrocytes expressing full-length L1 promoted neurite outgrowth and neuronal cell migration in vitro. Because the vector system can be used to confer phenotypic changes in primary neural cells, it will be useful to promote regeneration in vivo in central nervous system.
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