Cell-autonomous regulation of epithelial cell quiescence by calcium channel Trpv6
- University of Michigan, United States
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
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Author details
Funding
National Science Foundation (IOS-1557850)
- Cunming Duan
National Science Foundation (IOS-1755262)
- Cunming Duan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All experiments were conducted in accordance with the protocol approved by the University of Michigan Institutional Committee on the Use and Care of Animals (Protocol # PRO00008801).
Copyright
© 2019, Xin et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Cell-autonomous regulation of epithelial cell quiescence by calcium channel Trpv6
eLife 8:e48003.
https://doi.org/10.7554/eLife.48003
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