1996 Fiscal Year Final Research Report Summary
Characterization of membrane protein complex associated with dystrophin
| Project/Area Number |
06454280
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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 |
SHIMIZU Teruo Teikyo University School of Medicine, Professor, 医学部, 教授 (00107666)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Fumiaki Teikyo University School of Medicine, Instructor, 医学部, 助手 (40286993)
YAMADA Hiroki Teikyo University School of Medicine, Instructor, 医学部, 助手 (90260926)
MATSUMURA Kiichiro Teikyo University School of Medicine, Associate Professor, 医学部, 助教授 (50260922)
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| Project Period (FY) |
1994 – 1996
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| Keywords | dystroglycan / laminin / Dp116 / utrophin / sarcoglycan |
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| Research Abstract |
In the present study, we have investigated the biological functions of the dystroglycan complex in the nervous system. As results, we show that the nervous system alpha-dystroglycan has a molecular mass of 120 kDa instead of 15kDa of that of muscle. The nervous system alpha-dystroglycan binds laminin with high affinity and this binding is dependent on calcium and is inhibited by heparin and NaCl. The nervous system alpha-dystroglycan is presumed to be associated with Dp116 and utrophin as anchoring proteins, but not the sarcoglycan complex. We also show that 120 kDa alpha-dystroglycan is a Schwann cell receptor of laminin-2, the endoneurial isoform of laminin comprised of the alpha2, beta1 and gamma1 chains, in the peripheral nervous system. Schwann cellalpha-dystroglycan is also a receptor of agrin, an acetylcholine receptor-aggregating molecule having partial homology to laminin alpha chains in the C-terminus. Immunochemical analysis demonstrates that the peripheral nerve isoform of agrin is a 400 kDa component of the endoneurial basal lamina and is co-localized with alpha-dystroglycan surrounding the outermost layr of myelin sheath of peripheral nerve fibers. Blot overlay analysis demonstrates that both endogenous peripheral nerve agrin and laminin-2 bind to Schwann cell alpha-dystroglycan. Recombinant C-terminal fragment of the peripheral nerve isoform of agrin also binds to Schwann cell alpha-dystroglycan, confirming that the binding site for Schwann cell alpha-dystroglycan resides in the C-terminus of agrinmolecule. Furthermore, the binding of recombinant agrin C-terminal fragment to Schwann cell alpha-dystroglycan competes with that of laminin-2. All together, these results indicate that alpha-dystroglycan is a dual receptor for agrin and laminin-2 in the Schwann cell membrane. Currently, we are investigating the biological functions of the dystroglycan complex in the central nervous system.
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[Publications] Higuchi, I., Yamada, H., Fukunaga, H., Iwaki, H., Okubo, R., Nakagawa, M., Osame, M., Roberds, S.L., Shimizu, T., Campbell, K.P., and Matsumura, K.: "Abnormal expression of laminin suggests disturbance of sarcolemma-extracellular matrix interaction in Japanese Patients with autosomal recessive muscular dystrophy deficient in adhalin." J.Clin.Invest.94. 601-606 (1994)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Toda, T., Watanabe, T., Matsumura.K., Sunada, Y., Yamada, H., Nakano, I., Mannen, T., Kanazawa, I., and Shimizu, T.: "Three-dimensional MR imaging of brain surface anomalies in Fukuyama-type congenital muscular dystrophy." Muscle Nerve. 18. 508-517 (1995)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yamada, H., Tome, F.M.S., Higuchi, I., Kawai, H., Azibi, K., chaouch, M., Roberds, S.L., Tanaka, T., Fujita, S., Mitusi, T., Fukunaga, H., Miyoshi, K., Osame, M., Fardeau, M., Kaplan, J-C., Shimizu, T., Campbell, K.P., and Matsumura, K.: "Laminin abnormality is severe childhood autosomal recessive muscular dystrophy." Lab.Invest.72. 715-722 (1995)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kawai, H., Akaike, M., Endo, T., Adachi, K., Inui, T., Mitsui, T., Kashiwagi, S., Fujiwara, T., Okuno, S., Shin, T., Miyoshi, K., Campbell, K.P., Yamada, H., Shimizu, T., Matsumura, K., and Saito, S.: "Adhalin gene mutations in patients with autosomal recessive childhood onset muscular dystrophy with adhalin deficiency." J.Clin.Invest.96. 1202-1207 (1995)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yamada, H., Hori, H., Tanaka, T., Fujita, S., Fukuta-Ohi, H., Hojo, S., Tamura, A., Shimizu, T., and Matsumura, K.: "Secretion of laminin alpha2 chain in cerebrospinal fluid." F.E.B.S.Lett.376. 37-40 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Yamada, H., Chiba, A., Endo, T., Kobata, A., Anderson, L.V.B., Hori, H., Fukuta-Ohi, H., Kanazawa, I., Campbell, K.P., Shimizu, T., and Matsumura, K.: "Characterization of dystroglycan-laminin interaction in peripheral nerve." J.Neurochem.66. 1518-1524 (1996)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yamada, H., Denzer, A., Hori, H., Tanaka, T., Anderson, L.V.B., Fujita, S., Fukuta-Ohi, H., Shimizu, T., Ruegg, M.A., and Matsumura, K.: "Dystroglycan is a dual receptor of agrin and laminin-2 in Schwann cell membrane." J.Biol.Chem.271. 23418-23423 (1996)
Description
「研究成果報告書概要(欧文)」より
