1999 Fiscal Year Final Research Report Summary
MOLECULAR MECHANISM OF PERIPHEARAL MYELINOGENESIS
| Project/Area Number |
10044319
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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 | 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) |
YAMADA Hiroki TEIKYO UNIVERSITY, DEPARTMENT OF NEUROLOGY, INSTRUCTOR, 医学部, 助手 (90260926)
SUNADA Yoshihide KAWASAKI MEDICAL SCHOOL, DEPARTMENT OF NEUROLOGY, PROFESSOR, 医学部, 教授 (00240713)
SHIMIZU Teruo TEIKYO UNIVERSITY, DEPARTMENT OF NEUROLOGY, PROFESSOR, 医学部, 教授 (00107666)
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| Project Period (FY) |
1998 – 1999
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| Keywords | dystroglycan complex / laminin-2 / myelinogenesis / cell adhesion molecule / Schwann cell / basal lamina |
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| Research Abstract |
In Schwann cells, the transmembrane glycoproteinβ-dystroglycan composes the dystroglycan complex, together with the extracellular glycoprotein α-dystroglycan which binds laminin-2, a major component of the Schwann cell basal lamina. In order to provide clues to the biological functions of the interaction of the dystroglycan complex with laminin-2 in peripheral nerve, the expression of β-dystroglycan and laminin-α2 chain was studied in rat sciatic nerves undergoing axonal degeneration and regeneration as well as in normal condition. In normal sciatic nerve, immunoreactivity for the cytoplasmic domain of β-dystroglycan was consistently and selectively localized in the Schwann cell cytoplasm underlying the outer (abaxonal) membrane apposing the basal lamina. While β-dystroglycan expression was gradually downregulated in Schwann cells losing contact with axons during axonal degeneration, it was progressively upregulated as the regenerating process of ensheathment and myelination proceeded during regeneration. Interestingly, β-dystroglycan expression, when detectable, was always restricted to the Schwann cell cytoplasm beneath the outer membrane apposing the basal lamina during both axonal degeneration and regeneration. Furthermore, laminin-α2 immunoreactivity roughly paralleled that of β-dystroglycan during both axonal degeneration and regeneration, indicating that the expression of β-dystroglycan and laminin-α2 is induced and maintained by the Schwann cell contact with axons. Our results indicate that the dystroglycan complex is involved in the adhesion of the Schwann cell outer membrane with the basal lamina and suggest that the dystroglycan complex may play a role in the process of Schwann cell ensheathment and myelination through the interaction with laminin-2.
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[Publications] Sasaki, T., Yamada, H., Matsumura, K., Shimizu, T., Kobata, A. and Endo, T.: "Detection of O-mannosyl glycans in rabbit skeletal muscle α-dyslroglycan"Biochim. Biophys. Acta.. 1425. 599-606 (1998)
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[Publications] Kobayashi, K., Nakahori, Y., Miyake, M., Matsumura, K., Kondo-Iida, E., Nomura, Y., Segawa, M,, Yoshioka, M, Saito, K,, Osawa, M., Hamano, K., Sakakibara, Y., Nonaka, I., Nakagome, Y., Kanazawa, I., Nakamura, Y,, Tokunaga, K., and Toda, T.: "An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy."Nature. 394. 388-392 (1998)
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[Publications] Saito, F., Masaki, T., Kamakura, K., Anderson, L. V. B., Fujita, S., Fukuta-Ohi H., Sunada, Y,, Shimizu, T. and Matsumura, K.: "Characterization of the transmembrane molecular architecture of the dystroglycan complex in Schwann cells."J. Biol. Chem.. 274. 8240-8246 (199)
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[Publications] Matsumura, K., Saito, F., Yamada, H., Hase, A., Sunada, Y. and Shimizu, T.: "Sarcoglycan complex: a muscular supporter of dyslroglycan -dystrophin interplay?"Cell Molec. Biol.. 45. 751-762 (1999)
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