| Project/Area Number |
08457195
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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 |
Neurology
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| Research Institution | TEIKYO UNIVERSITY |
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Principal Investigator |
MATSUMURA Kiichiro TEIKYO UNIVERSITY,DEPARTMENT OF NEUROLOGY,ASSOCIATE PROFESSOR, 医学部, 助教授 (50260922)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Fumiaki TEIKYO UNIVERSITY,DEPARTMENT OF NEUROLOGY,INSTRUCTOR, 医学部, 助手 (40286993)
YAMADA Hiroki TEIKYO UNIVERSITY,DEPARTMENT OF NEUROLOGY,INSTRUCTOR (90260926)
萩原 宏毅 帝京大学, 医学部, 助手 (80276732)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 1998: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1996: ¥3,500,000 (Direct Cost: ¥3,500,000)
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| Keywords | Dystroglycan / Laminin / Agrin / Dystrophin / Dp116 / Cell adhesion / Schwann cell |
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| Research Abstract |
Duchenne muscular dystrophy (DMD) is an X-linked recessive, lethal neuromuscular disease. The gene defect causing DMD was identified in 1987 and the causative protein was named dystrophin. Over the last 10 years, dystrophin was clarified to be a cytoskeletal protein complexed with a number of cell membrane glycoproteins, including dystroglycan, to form the dystrophin-glycoprotein complex. Dystroglycan. is encoded by a single gene and cleaved into two proteins alpha- and beta-dystroglycan by posttranslational processing. To begin to elucidate the physiological functions of dystroglycan, we performed biochemical and cell biological characterization of dystroglycan in skeletal muscle and peripheral nerve. We obtained results that inidicate the following : (1) The dystroglycan complex, but not the sarcoglycan complex, is expressed in peripheral nerve. (2) x-dystroglycan is an extracellular laminin- and agrin-binding protein anchored to the cell membrane by a transmembrane protein beta-dystroglycan in Schwann cells. (3) Glycosylation, sialylation in particular, of cz-dystroglycan mediates the binding of laminin-1 and 2 to alpha-dystroglycan. (4) The cytoplasmic domain of beta-dystroglycan is anchored to Dpi 16, an dystrophin isoform, mainly via the 15 C-terminal amino acids of its cytoplasmic domain in Schwann cells. We also characterized the role of dystroglycan in the adhesion of schwannoma cells to laminin and found that dystroglycan plays an important role in the adhesion to lam mm. All together, our results support a role for dystroglycan as a major cell adhesion molecule in the cell membrane of not only skeletal muscle but also Schwann cells. Since the deficiency of laminin-2 causes peripheral nerve dysmyelination in the patient with a subset of congenital muscular dystrophy and dy mice, we propose that the interaction of laminin-2 with dystroglycan plays an important role in the Schwann cell myelinogenesis.
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