PUBLICATION
A calcineurin-mediated scaling mechanism that controls a K+-leak channel to regulate morphogen and growth factor transcription
- Authors
- Yi, C., Spitters, T.W., Al-Far, E.A.A., Wang, S., Xiong, T., Cai, S., Yan, X., Guan, K., Wagner, M., El-Armouche, A., Antos, C.L.
- ID
- ZDB-PUB-210409-18
- Date
- 2021
- Source
- eLIFE 10: (Journal)
- Registered Authors
- Antos, Christopher
- Keywords
- developmental biology, zebrafish
- MeSH Terms
-
- Male
- Humans
- HeLa Cells
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Membrane Potentials
- Calcineurin/genetics
- Calcineurin/metabolism*
- Intercellular Signaling Peptides and Proteins/genetics
- Intercellular Signaling Peptides and Proteins/metabolism*
- Morphogenesis
- Phosphorylation
- Animal Fins/embryology
- Animal Fins/growth & development
- Animal Fins/metabolism*
- Female
- Protein Processing, Post-Translational
- Hedgehog Proteins/genetics
- Hedgehog Proteins/metabolism
- Animals, Genetically Modified
- Transcription, Genetic*
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/growth & development
- Zebrafish/metabolism*
- HEK293 Cells
- Potassium/metabolism*
- Animals
- Potassium Channels, Tandem Pore Domain/genetics
- Potassium Channels, Tandem Pore Domain/metabolism*
- Ion Channel Gating
- Transcription Factors/genetics
- Transcription Factors/metabolism
- PubMed
- 33830014 Full text @ Elife
Citation
Yi, C., Spitters, T.W., Al-Far, E.A.A., Wang, S., Xiong, T., Cai, S., Yan, X., Guan, K., Wagner, M., El-Armouche, A., Antos, C.L. (2021) A calcineurin-mediated scaling mechanism that controls a K+-leak channel to regulate morphogen and growth factor transcription. eLIFE. 10:.
Abstract
The increase in activity of the two-pore potassium-leak channel Kcnk5b maintains allometric juvenile growth of adult zebrafish appendages. However, it remains unknown how this channel maintains allometric growth and how its bioelectric activity is regulated to scale these anatomical structures. We show the activation of Kcnk5b is sufficient to activate several genes that are part of important development programs. We provide in vivo transplantation evidence that the activation of gene transcription is cell autonomous. We also show that Kcnk5b will induce the expression of different subsets of the tested developmental genes in different cultured mammalian cell lines, which may explain how one electrophysiological stimulus can coordinately regulate the allometric growth of diverse populations of cells in the fin that use different developmental signals. We also provide evidence that the post-translational modification of serine 345 in Kcnk5b by calcineurin regulates channel activity to scale the fin. Thus, we show how an endogenous bioelectric mechanism can be regulated to promote coordinated developmental signaling to generate and scale a vertebrate appendage.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping