PUBLICATION
Cell-autonomous regulation of epithelial cell quiescence by calcium channel Trpv6
- Authors
- Xin, Y., Malick, A., Hu, M., Liu, C., Batah, H., Xu, H., Duan, C.
- ID
- ZDB-PUB-190919-2
- Date
- 2019
- Source
- eLIFE 8: (Journal)
- Registered Authors
- Duan, Cunming
- Keywords
- developmental biology, zebrafish
- MeSH Terms
-
- TRPV Cation Channels/deficiency
- TRPV Cation Channels/metabolism*
- Gene Deletion
- Epithelial Cells/physiology*
- Signal Transduction
- Cell Proliferation*
- Humans
- Intercellular Signaling Peptides and Proteins/metabolism
- Zebrafish
- Animals
- Calcium/metabolism
- Zebrafish Proteins/deficiency
- Zebrafish Proteins/metabolism
- Calcium Channels/metabolism*
- PubMed
- 31526479 Full text @ Elife
Citation
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:.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping