ZFIN ID: ZDB-PUB-190919-2
Cell-autonomous regulation of epithelial cell quiescence by calcium channel Trpv6
Xin, Y., Malick, A., Hu, M., Liu, C., Batah, H., Xu, H., Duan, C.
Date: 2019
Source: eLIFE   8: (Journal)
Registered Authors: Duan, Cunming
Keywords: developmental biology, zebrafish
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
PubMed: 31526479 Full text @ Elife
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ABSTRACT
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.
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