1. Academic Validation
  2. The chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) controls cellular quiescence by hyperpolarizing the cell membrane during diapause in the crustacean Artemia

The chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) controls cellular quiescence by hyperpolarizing the cell membrane during diapause in the crustacean Artemia

  • J Biol Chem. 2019 Apr 19;294(16):6598-6611. doi: 10.1074/jbc.RA118.005900.
An-Qi Li 1 Zhan-Peng Sun 1 Xu Liu 1 Jin-Shu Yang 1 Feng Jin 1 Lin Zhu 1 Wen-Huan Jia 1 Stephanie De Vos 2 Gilbert Van Stappen 2 Peter Bossier 2 Wei-Jun Yang 3 4
Affiliations

Affiliations

  • 1 From the College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • 2 the Laboratory of Aquaculture and Artemia Reference Center, Department of Animal Production, Ghent University, B-9000 Ghent, Belgium, and.
  • 3 From the College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China, w_jyang@zju.edu.cn.
  • 4 the Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266000, China.
Abstract

Cellular quiescence, a reversible state in which growth, proliferation, and other cellular activities are arrested, is important for self-renewal, differentiation, development, regeneration, and stress resistance. However, the physiological mechanisms underlying cellular quiescence remain largely unknown. In the present study, we used embryos of the crustacean Artemia in the diapause stage, in which these embryos remain quiescent for prolonged periods, as a model to explore the relationship between cell-membrane potential (Vmem) and quiescence. We found that Vmem is hyperpolarized and that the intracellular chloride concentration is high in diapause embryos, whereas Vmem is depolarized and intracellular chloride concentration is reduced in postdiapause embryos and during further embryonic development. We identified and characterized the chloride ion channel protein cystic fibrosis transmembrane conductance regulator (CFTR) of Artemia (Ar-CFTR) and found that its expression is silenced in quiescent cells of Artemia diapause embryos but remains constant in all other embryonic stages. Ar-CFTR knockdown and GlyH-101-mediated chemical inhibition of Ar-CFTR produced diapause embryos having a high Vmem and intracellular chloride concentration, whereas control Artemia embryos released free-swimming nauplius larvae. Transcriptome analysis of embryos at different developmental stages revealed that proliferation, differentiation, and metabolism are suppressed in diapause embryos and restored in postdiapause embryos. Combined with RNA Sequencing (RNA-Seq) of GlyH-101-treated MCF-7 breast Cancer cells, these analyses revealed that CFTR inhibition down-regulates the Wnt and Aurora Kinase A (AURKA) signaling pathways and up-regulates the p53 signaling pathway. Our findings provide insight into CFTR-mediated regulation of cellular quiescence and Vmem in the Artemia model.

Keywords

Artemia; cell cycle; cell proliferation; cellular quiescence; channel activation; chloride channel; cystic fibrosis transmembrane conductance regulator (CFTR); diapause embryo; dormancy maintenance; hyperpolarization.

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