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标题：Intracellular TMEM16A is necessary for myogenesis of skeletal muscle
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作者：Wen Yuan ; Cong-Cong Cui ; Jing Li 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：11
页码：1-17
DOI：10.1016/j.isci.2022.105446
语种：English
出版社：Elsevier
摘要：SummaryTransmembrane protein 16A (TMEM16A) localizes at plasma membrane and controls chloride influx in various type of cells. We here showed an intracellular localization pattern of TMEM16A molecules. In myoblasts, TMEM16A was primarily localized to the cytosolic compartment and partially co-localized with intracellular organelles. The global deletion of TMEM16A led to severe skeletal muscle developmental defect.In vitroobservation showed that the proliferation ofTmem16a−/− myoblasts was significantly promoted along with activated ERK1/2 and Cyclin D expression; the myogenic differentiation was impaired accompanied by the enhanced caspase 12/3 activation, implying enhanced endoplasmic reticulum (ER) stress. Interestingly, the bradykinin-induced Ca2+release from ER calcium store was significantly enhanced after TMEM16A deletion. This suggested a suppressing role of intracellular TMEM16A in ER calcium release whereby regulating the flux of chloride ion across the ER membrane. Our findings reveal a unique location pattern of TMEM16A in undifferentiated myoblasts and its role in myogenesis.Graphical abstractDisplay OmittedHighlights•TMEM16A locates to the intracellular organelles of undifferentiated myoblast•Intracellular TMEM16A modulates IP3R calcium channels-mediated Ca2+release•Intracellular TMEM16A is necessary for skeletal muscle developmentMolecular biology; Cell biology