The significance of calpain protease activity in skeletal muscle cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 19H04014
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59020:Sports sciences-related
• Research Institution: National Agriculture and Food Research Organization
• Principal Investigator: Koichi Ojima 国立研究開発法人農業・食品産業技術総合研究機構, 畜産研究部門, 上級研究員 (60415544)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 骨格筋 / カルパイン

Outline of Final Research Achievements

Calpains are Ca2+-requiring intracellular proteases. Skeletal muscle cells express three types of calpain, calpain-1 and calpain-2, ubiquitously expressed in mammalian cells, and skeletal muscle-specific calpain-3. It is known that the protease activity of calpain-3 is required for muscle stress response. However, the physiological significance of calpain-3’s proteolysis in response to muscle stress is not fully understood. We demonstrated that the N-terminal region of calpain-3 was cleaved by calpain-1 and calpain-2. Meanwhile, calpain-3 preferentially cleaved the N-terminus of calpain-1 over that of calpain-2. These results indicate the reciprocal relation among calpain-1, -2, and -3 in skeletal muscle cells. Our findings suggest that calpain-3 proteolysis against muscle exercise is involved in the inter-calpain network to prime proteolysis of calpain-1 and/or calpain-2.

Free Research Field

骨格筋細胞生物学

Academic Significance and Societal Importance of the Research Achievements

カルパインは組織普遍的あるいは組織特異的に発現するタイプがあり、ヒトでは15種類存在する。骨格筋細胞でカルパイン1, 2,および3が発現することが知られていたが、3種類のカルパインが同一細胞内に存在する意義は不明であった。本研究では、骨格筋細胞内に共存するカルパイン1、2、3間には切断酵素と基質の関係があることを示し、骨格筋細胞内に異なる種類のカルパインが発現する意義を説明することが可能となった。