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bioRxiv · 10.1101/631861

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.
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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 and Tor signaling. In zebrafish epithelia and human colon cancer 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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Xin, Y., Malick, A., Hu, M., Liu, C., Batah, H., Xu, H., Duan, C.. 2019-05-08. Cell-autonomous regulation of epithelial cell quiescence by calcium channel Trpv6. https://doi.org/10.1101/631861

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