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