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
Affiliations
Wen Yuan
The Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Sciences, Nanjing Normal University, Nanjing 210023, China
Cong-Cong Cui
The Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Sciences, Nanjing Normal University, Nanjing 210023, China
Jing Li
The Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Sciences, Nanjing Normal University, Nanjing 210023, China
Yan-Hua Xu
The Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Sciences, Nanjing Normal University, Nanjing 210023, China
Chun-E Fan
The Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Sciences, Nanjing Normal University, Nanjing 210023, China
Yu-Chen Chen
The Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Sciences, Nanjing Normal University, Nanjing 210023, China
Hong-Wei Fan
The Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Sciences, Nanjing Normal University, Nanjing 210023, China
Bing-Xue Hu
The Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Sciences, Nanjing Normal University, Nanjing 210023, China
Mei-Yun Shi
The Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Sciences, Nanjing Normal University, Nanjing 210023, China
Zhi-Yuan Sun
The Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Sciences, Nanjing Normal University, Nanjing 210023, China
Pei Wang
State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing 210008, China
Teng-Xiang Ma
The Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Sciences, Nanjing Normal University, Nanjing 210023, China
Zhao Zhang
The Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Sciences, Nanjing Normal University, Nanjing 210023, China
Min-Sheng Zhu
State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing 210008, China
Hua-Qun Chen
The Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Sciences, Nanjing Normal University, Nanjing 210023, China; Corresponding author
Summary: 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.
