PUBLICATION
Regulation of cell quiescence-proliferation balance by Ca2+-CaMKK-Akt signaling
- Authors
- Xin, Y., Guan, J., Li, Y., Duan, C.
- ID
- ZDB-PUB-210922-25
- Date
- 2021
- Source
- Journal of Cell Science 134(20): (Journal)
- Registered Authors
- Duan, Cunming
- Keywords
- Calmodulin, Cell cycle, ER Ca2+, Intracellular Ca2+, Ionocyte, Trpv6, Zebrafish
- MeSH Terms
-
- Animals
- Calcium
- Calcium-Calmodulin-Dependent Protein Kinase Kinase*
- Cell Proliferation
- Proto-Oncogene Proteins c-akt*/genetics
- Zebrafish/genetics
- PubMed
- 34545403 Full text @ J. Cell Sci.
Citation
Xin, Y., Guan, J., Li, Y., Duan, C. (2021) Regulation of cell quiescence-proliferation balance by Ca2+-CaMKK-Akt signaling. Journal of Cell Science. 134(20):.
Abstract
Compared with our extensive understanding of the cell cycle, we have limited knowledge of how the cell quiescence-proliferation decision is regulated. Using a zebrafish epithelial model, we report a novel signaling mechanism governing the cell quiescence-proliferation decision. Zebrafish Ca2+-transporting epithelial cells or ionocytes maintain high cytoplasmic Ca2+ levels ([Ca2+]c) due to the expression of Trpv6. Genetic deletion, pharmacological inhibition of Trpv6 or reducing external Ca2+ lowered the [Ca2+]c and reactivated these cells. The ionocyte reactivation was attenuated by chelating intracellular Ca2+ and inhibiting calmodulin (CaM), suggesting a Ca2+/CaM-dependent mechanism at work. Ling-term imaging studies showed that after an initial decrease, [Ca2+]c gradually returned to the basal levels. There was a concomitant decease in ER Ca2+ levels. Lowering the ER Ca2+ store content or inhibiting ryanodine receptors impaired ionocyte reactivation. Further analyses suggest that CaMKK is a key molecular link between Ca2+ and Akt signaling. Genetic deletion or inhibition of CaMKK abolished and expression of a constitutively active Akt rescued cell reactivation. These results suggest that the quiescence-proliferation decision in zebrafish ionocytes is regulated by Trpv6-mediated Ca2+ and CaMKK-Akt signaling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping