A calcineurin-mediated scaling mechanism that controls a K+-leak channel to regulate morphogen and growth factor transcription
Chao Yi,
Tim WGM Spitters,
Ezz Al-Din Ahmed Al-Far,
Sen Wang,
TianLong Xiong,
Simian Cai,
Xin Yan,
Kaomei Guan,
Michael Wagner,
Ali El-Armouche,
Christopher L Antos
Affiliations
Chao Yi
School of Life Sciences and Technology, ShanghaiTech University, Shanghai, China; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China
Tim WGM Spitters
School of Life Sciences and Technology, ShanghaiTech University, Shanghai, China
Ezz Al-Din Ahmed Al-Far
Institut für Pharmakologie und Toxikologie, Technische Universität Dresden, Dresden, Germany
Sen Wang
School of Life Sciences and Technology, ShanghaiTech University, Shanghai, China; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China
TianLong Xiong
School of Life Sciences and Technology, ShanghaiTech University, Shanghai, China; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China
Simian Cai
School of Life Sciences and Technology, ShanghaiTech University, Shanghai, China
Xin Yan
School of Life Sciences and Technology, ShanghaiTech University, Shanghai, China
Kaomei Guan
Institut für Pharmakologie und Toxikologie, Technische Universität Dresden, Dresden, Germany
Michael Wagner
Institut für Pharmakologie und Toxikologie, Technische Universität Dresden, Dresden, Germany; Klinik für Innere Medizin und Kardiologie, Herzzentrum Dresden, Technische Universität Dresden, Dresden, Germany
Ali El-Armouche
Institut für Pharmakologie und Toxikologie, Technische Universität Dresden, Dresden, Germany
School of Life Sciences and Technology, ShanghaiTech University, Shanghai, China; Institut für Pharmakologie und Toxikologie, Technische Universität Dresden, Dresden, Germany
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.
