Elucidation of the mechanism of N-WASP-Nebl complex activation during cardiomyocyte hypertrophy

2016 Fiscal Year Final Research Report

• Project/Area Number: 26440045
• 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, 大学院融合科学研究科, 助教 (60466860)
• Co-Investigator(Renkei-kenkyūsha): ENDO TAKESHI 千葉大学, 大学院理学研究科, 教授 (30194038) ; TAKANO HARUKO 千葉大学, 大学院医学研究院, 学振PD (40532891)
• Research Collaborator: HISAMITSU SHOSHI 千葉大学, 理学部・生物学科, 学部生 ; KURIHARA YUSUKE 千葉大学, 理学部・生物学科, 学部生
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 筋原線維形成 / アクチン重合 / N-WASP / nebulette / 心筋 / 筋肥大

Outline of Final Research Achievements

Striated muscle hypertrophy is necessary for adaptation to mechanical stress increases by growth, exercise and disease conditions. Muscle hypertrophy requires myofibrilogenesis, however, the mechanism of miyofibrillogenesis has been obscure. In this study, we focused on that N-WASP interacts stably with nebulette (Nebl), a cardiac specific nebulin family protein. Thus, the activity of N-WASP-Nebl complex seemed to be regulated in vivo. First, we showed that actin monomer is incorporated into Z-band of myofibrils in cardiac muscle in vivo. We also identified Amph2 as one of the N-WASP-binding proteins in cardiac muscle. Furthermore, cardiac muscle specific inducible N-WASP knockout mice exhibited symptoms of dilated cardiac hypertrophy. Taken together, these results suggest that N-WASP is involved in cardiac muscle maintenance by regulating myofibrillogenesis.

Free Research Field

分子細胞生物学