Elucidation of mechanism of the nuclear arrangement regulation by N-WASP and membrane deforming protein during skeletal muscle regeneration

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07328
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Chiba University
• Principal Investigator: Takano Kazunori 千葉大学, 大学院理学研究院, 助教 (60466860)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 筋再生 / 周辺核 / N-WASP / Amphiphysin2 / 核動態 / 膜変形 / アクチン

Outline of Final Research Achievements

The skeletal muscle maturation process is an important phenomenon in elucidating the mechanism of muscle regeneration and disease development. In multinucleated skeletal muscle cells, the nuclei arranged in a line at the center (central nucleus) move to just near the plasma membrane (PM) during the maturation process, but the mechanism of this peripheral nucleation is unknown. To clarify the role of N-WASP in peripheral movement of nucleus, we investigated the regulatory mechanism of nuclear export of N-WASP during the skeletal muscle maturation and the molecular mechanism of the peripheral movement of nucleus by the cooperative action of N-WASP and Amph2. Our results suggest that actin regulation by the N-WASP-Amph2 axis may function as a guide for determining the direction of nucleus to move peripherally.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

多くの骨格筋形成に関わるタンパク質の遺伝子変異は中心核病などの筋疾患に直結する。しかしながら，中心核病の表現型は原因となる遺伝子変異の結果として起こるにも関わらず，中心核病の原因遺伝子であるAmph2とN-WASPの周辺核化機構に果たす役割は依然として不明のままである。このため，中心核病の病因がアクチン細胞骨格の制御と細胞膜の変形の協調作用の破綻である可能性を示した点で本研究は学術的意義がある。