Therapeutic strategy for muscular dystrophy via regulation of STIM1 mediated Ca2+ homeostasis

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09328
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Teikyo University
• Principal Investigator: Shimizu Teruo 帝京大学, 医療技術学部, 特任教授 (00107666)
• Co-Investigator(Kenkyū-buntansha): 真先 敏弘 帝京科学大学, 医療科学部, 教授 (00585028) ; 萩原 宏毅 帝京科学大学, 医療科学部, 教授 (80276732)
• Co-Investigator(Renkei-kenkyūsha): Matsumura Kiichiro 帝京大学, 医学部, 教授 (50260922) ; Saito Fumiaki 帝京大学, 医学部, 准教授 (40286993)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 筋ジストロフィー / 細管集合体ミオパチー / カルシウムホメオスタシス / STIM1 / ORAI1

Outline of Final Research Achievements

Recently, STIM1-ORAI1 signaling is receiving attention as molecules regulating calcium homeostasis in skeletal muscle. In this study, we investigated the pathomechanism of a novel mutation of STIM1 we identified in a family with tubular aggregate myopathy. In contrast to the previous reports, this novel mutation resides in the cytoplasmic domain of STIM1. Gene transfer experiments using cultured myoblasts exhibit that the mutant STIM1 induces marked reduction of intracellular calcium concentration and inhibits puncta formation of STIM1 with tapsigargin, which is necessary for ORAI1 activation. Taken together, in the family with the novel mutation, tubular aggregate myopathy is caused by a distinct pathomechanism from that previously proposed, i.e. excessive influx of calcium.

Free Research Field

神経内科学