Elucidation of the molecular network that controls myelination

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07127
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Miyamoto Yuki 国立研究開発法人国立成育医療研究センター, 薬剤治療研究部, 研究員 (50425708)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ミエリン / オリゴデンドロサイト / 共培養 / ミエリン変性症

Outline of Final Research Achievements

During development of the nervous system in mammals, myelin-forming cells wrap their plasma membranes around neuronal axons, forming multiple myelin sheaths. Arf1 is a small guanosine triphosphate-binding protein that plays multiple roles in intracellular trafficking and related signaling, We demonstrate that the Arf1 guanine nucleotide exchange factor, BIG1, and the effector Arf1 regulate the initiation of myelination of axons by Schwann cells. Schwann cell-specific BIG1 conditional knockout mice, which have been generated here, exhibit reduced myelin thickness and decreased localization of myelin protein zero in the myelin membrane, compared with their littermate controls. Similar results in myelin thickness are observed in Arf1 conditional knockout mice, which have also been generated here. Thus, the BIG1 and Arf1 unit plays a key role in Schwann cell myelination, newly adding it to the list of molecular units controlling myelination.

Free Research Field

分子神経科学

Academic Significance and Societal Importance of the Research Achievements

神経科学の分野で、ミエリン形成細胞を対象とした研究は国内外において非常に少ない。しかし、近年、筋萎縮性側索硬化症やアルツハイマー型認知症においてミエリン構造の異常が明らかとなってきたように、今後神経変性症などの創薬ターゲットとしてミエリン形成細胞が脚光を浴びることは想像に難くない。本研究では、研究人口の少ないミエリン形成細胞を対象とし、中でも未知の部分が多いミエリン発生期を司る分子機構について研究を行ったものである。