| Project/Area Number |
11670644
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 |
KOBAYASHI Michiko TEIKYO UNIVERSITY, DEPARTMENT OF NEUROLOGY, INSTRUCTOR, 医学部, 助手 (00312009)
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| Co-Investigator(Kenkyū-buntansha) |
HASE Asako TEIKYO UNIVERSITY, DEPARTMENT OF NEUROLOGY, INSTRUCTOR, 医学部, 助手 (90328039)
YAMADA Hiroki TEIKYO UNIVERSITY, DEPARTMENT OF NEUROLOGY, INSTRUCTOR, 医学部, 助手 (90260926)
MATSUMURA Kiichiro TEIKYO UNIVERSITY, DEPARTMENT OF NEUROLOGY, ASSOCIATE PROFESSOR, 医学部, 助教授 (50260922)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | sarcoglycanopathy / sarcoglycan complex / dystroglycan complex / basal lamina / laminin-2 |
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| Research Abstract |
Severe limb girdle muscular dystrophy called sarcoglycanopathy is caused by the deficiency of the sarcoglycan complex. The molecular pathogenesis how the deficiency of the sarcoglycan complex leads to muscle cell death remains unknown. We have hypothesized that the deficiency of the sarcoglycan complex causes the fragility of the dystroglycan complex, which in turn leads to sarcolemmal instability. In this study, we investigated (1) the cytoskeletal element that anchors the dystroglycan complex in non-muslce cells and (2) the stability of the dystroglycan complex in non-muscle cells lacking the sarcoglycan complex. Small sized isoforms of dystrophin were co-localized with the cytoplasmic domain of β-dystroglycan in the cell membrane of non-muscle cells. Furthermore, small sized isoforms of dystrophin bound to the cytoplasmic domain of β-dystroglycan. The 15 C-terminal amino acids of the cytoplasmic domain of β-dystroglycan were involved in the high affinity binding of small sized isoforms of dystrophin, but they were not solely responsible for the interaction of β-dystroglycan. Interestingly, the β-dystroglycan-precipitating antibody precipitated only a small fraction of α-dystroglycan and did not precipitate detectable amount of laminin or small sized isoforms of dystrophin from the non-muscle cell extracts. We propose that (1) small sized isoforms of dystrophin anchor β-dystroglycan in non-muscle cells in vivo, and (2) the non-muscle cell dystroglycan complex is fragile due to the absence of the sarcoglycan complex. These results support our hypothesis that the deficiency of the sarcoglycan complex causes the fragility of the dystroglycan complex and leads to the instability of the sarcolemma.
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