Intracellular TMEM16A is necessary for myogenesis of skeletal muscle

Wen Yuan; Cong-Cong Cui; Jing Li; Yan-Hua Xu; Chun-E Fan; Yu-Chen Chen; Hong-Wei Fan; Bing-Xue Hu; Mei-Yun Shi; Zhi-Yuan Sun; Pei Wang; Teng-Xiang Ma; Zhao Zhang; Min-Sheng Zhu; Hua-Qun Chen

doi:10.1016/j.isci.2022.105446

Intracellular TMEM16A is necessary for myogenesis of skeletal muscle

iScience. 2022 Nov 8;25(11):105446. doi: 10.1016/j.isci.2022.105446. eCollection 2022 Nov 18.

Authors

Affiliations

¹ The Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
² State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing 210008, China.

Abstract

Transmembrane 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 vitro observation showed that the proliferation of Tmem16a-/- 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.

Keywords: Cell biology; Molecular biology.