| Project/Area Number |
04454159
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Keio University |
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Principal Investigator |
UYEMURA Keiichi Dept of Physiology, Keio Univ.School of Med.Professor, 医学部, 教授 (90049792)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Kayoko Dept of Physiology, Keio Univ.School of Med.Instructor, 医学部, 助手 (30193246)
MIURA Masayuki Dept of Physiology, Keio Univ.School of Med.Instructor, 医学部, 助手 (50202338)
TAKEDA Yasuo Dept of Physiology, Keio Univ.School of Med.Instructor, 医学部, 助手 (60245462)
OKAMOTA Hitoshi Dept of Physiology, Keio Univ.School of Med.Assistant Professor, 医学部, 講師 (40183769)
ASOU Hiroaki Dept of Physiology, Keio Univ.School of Med.Assistant Professor, 医学部, 講師 (30104160)
矢崎 貴仁 慶應義塾大学, 医学部, 助手 (80200484)
白尾 智明 慶應義塾大学, 医学部, 助教授 (20171043)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1994: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1993: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1992: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | L1 protein / Immunoglobulin superfamily / cell adhesion / neurite extension / neuronal migration / Schwann cell / hereditary neuropathy / PO protein / L1 / PO / 細胞接着 / 神経細胞 / ミエリン / Charcot-Marie-Tooth病 / アイソフォーム / モノクローナル抗体 / サブプレート / 神経突起伸展 / P0 / 接着性蛋白 |
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| Research Abstract |
L1 protein is a large multifunctional glycoprotein of immunoglobulin superfamily in nervous system.The mutations of L1 gene induce disorders of brain morphogenesis or metal development. We studied structure and function of L1 and related proteins and obtained following results.
1) We established the permanent L cell lines expressing L1 by transfection of L1cDNA.The L1 expressing cells showed homophilic cell adhesion resulting to increase intracellular calcium level by opening of calcium channels. In the coculture with reaggregates of cerebellar neurons, L1 expressing cells promoted neurite extension, growth cone development and neuronal migration.
2) In addition to the complete from of L1 in neurons, we found a new mRNA of L1 isoform (L1s) lacking 2 short exons, which was excusively expressed in non-neuronal cells such as Schwann cells. By the functional assay, the activity to promote neuronal migration of L1s protein was clearly lower than that of L1.
3) The 80 kDa molecule produced by L1 degradation showed inhibition of cell adhesion, which suggested functional change of L1 molecule in the course of development.
4) While PO protein showed homophilic adhesion and neurite outgrowth promotion, the each active site was suggested to be different each other. After the amino acid sequence of human PO protein was deduced by cDNA cloning, the chromosomal localization of PO gene was determined to be 1q22-23. The point mutations of PO gene were found in the families of Charcot-Marie-Tooth disease 1B,a hereditary neuropathy.
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