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

eLife

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[1] Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, United States;

关键词: IGF1 receptor;    Akt;    Tor;    PP2A;    Ca2+ signaling;    Erk;    Zebrafish;   

DOI  :  10.7554/eLife.48003

来源: publisher

【 摘 要 】

10.7554/eLife.48003.001Epithelial 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.

【 授权许可】

CC BY