Cell-autonomous regulation of epithelial cell quiescence by calcium channel Trpv6

Elife. 2019 Sep 17;8:e48003. doi: 10.7554/eLife.48003.


Epithelial homeostasis and regeneration require a pool of quiescent cells. How the quiescent cells are established and maintained is poorly understood. Here, we report that Trpv6, a cation channel responsible for epithelial Ca2+ absorption, functions as a key regulator of cellular quiescence. Genetic deletion and pharmacological blockade of Trpv6 promoted zebrafish epithelial cells to exit from quiescence and re-enter the cell cycle. Reintroducing Trpv6, but not its channel dead mutant, restored the quiescent state. Ca2+ imaging showed that Trpv6 is constitutively open in vivo. Mechanistically, Trpv6-mediated Ca2+ influx maintained the quiescent state by suppressing insulin-like growth factor (IGF)-mediated Akt-Tor and Erk signaling. In zebrafish epithelia and human colon carcinoma cells, Trpv6/TRPV6 elevated intracellular Ca2+ levels and activated PP2A, which down-regulated IGF signaling and promoted the quiescent state. Our findings suggest that Trpv6 mediates constitutive Ca2+ influx into epithelial cells to continuously suppress growth factor signaling and maintain the quiescent state.

Keywords: Akt; Ca2+ signaling; Erk; IGF1 receptor; PP2A; Tor; developmental biology; zebrafish.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channels / metabolism*
  • Cell Proliferation*
  • Epithelial Cells / physiology*
  • Gene Deletion
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Signal Transduction
  • TRPV Cation Channels / deficiency
  • TRPV Cation Channels / metabolism*
  • Zebrafish
  • Zebrafish Proteins / deficiency
  • Zebrafish Proteins / metabolism


  • Calcium Channels
  • Intercellular Signaling Peptides and Proteins
  • TRPV Cation Channels
  • TRPV6 protein, human
  • Zebrafish Proteins
  • trpv6 protein, zebrafish
  • Calcium