TY - JOUR TI - A calcineurin-mediated scaling mechanism that controls a K+-leak channel to regulate morphogen and growth factor transcription AU - Yi, Chao AU - Spitters, Tim WGM AU - Al-Far, Ezz Al-Din Ahmed AU - Wang, Sen AU - Xiong, TianLong AU - Cai, Simian AU - Yan, Xin AU - Guan, Kaomei AU - Wagner, Michael AU - El-Armouche, Ali AU - Antos, Christopher L A2 - Solnica-Krezel, Lilianna A2 - Bronner, Marianne E A2 - Solnica-Krezel, Lilianna VL - 10 PY - 2021 DA - 2021/04/08 SP - e60691 C1 - eLife 2021;10:e60691 DO - 10.7554/eLife.60691 UR - https://doi.org/10.7554/eLife.60691 AB - 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. KW - potassium channel KW - electrophysiology KW - tissue scaling KW - proportional growth KW - transcription KW - calcineurin JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -