The potassium channel KCNJ13 is essential for smooth muscle cytoskeletal organization during mouse tracheal tubulogenesis

Nature Communications
Wenguang YinDidier Y R Stainier

Abstract

Tubulogenesis is essential for the formation and function of internal organs. One such organ is the trachea, which allows gas exchange between the external environment and the lungs. However, the cellular and molecular mechanisms underlying tracheal tube development remain poorly understood. Here, we show that the potassium channel KCNJ13 is a critical modulator of tracheal tubulogenesis. We identify Kcnj13 in an ethylnitrosourea forward genetic screen for regulators of mouse respiratory organ development. Kcnj13 mutants exhibit a shorter trachea as well as defective smooth muscle (SM) cell alignment and polarity. KCNJ13 is essential to maintain ion homeostasis in tracheal SM cells, which is required for actin polymerization. This process appears to be mediated, at least in part, through activation of the actin regulator AKT, as pharmacological increase of AKT phosphorylation ameliorates the Kcnj13-mutant trachea phenotypes. These results provide insight into the role of ion homeostasis in cytoskeletal organization during tubulogenesis.

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Citations

Dec 24, 2018·The European Respiratory Journal·Wenguang YinDidier Y R Stainier
Nov 6, 2018·Nature Communications·Hyun-Taek KimDidier Y R Stainier
Aug 21, 2020·JCI Insight·Génesis VegaCarlos A Flores
Oct 10, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Ettore LignelliRory E Morty
Nov 30, 2019·Proceedings of the National Academy of Sciences of the United States of America·Hyun-Taek KimDidier Y R Stainier
Nov 17, 2020·Frontiers in Cell and Developmental Biology·Takuya YoshidaTsuyoshi Hirashima
Aug 24, 2019·Current Opinion in Genetics & Development·Jessica L Whited, Michael Levin
Apr 9, 2021·ERJ Open Research·Wenguang YinPixin Ran
Apr 8, 2021·American Journal of Physiology. Cell Physiology·C David Weaver, Jerod S Denton
Jun 29, 2021·IScience·Ting-Xin JiangCheng-Ming Chuong
Aug 14, 2021·The Journal of General Physiology·Ida BjörkgrenPolina V Lishko
Sep 4, 2021·Bioelectricity·Pranjal SrivastavaMichael Levin
Sep 25, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Martin R SilicGuangJun Zhang
Oct 26, 2021·Acta Biochimica Et Biophysica Sinica·Shishuai WenNing Qu

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Datasets Mentioned

BETA
GM130
AB5535

Methods Mentioned

BETA
genotyping
dissection
PCR
acetylation

Software Mentioned

CLCBio Genomic Workbench
Axio Imager
ImageJ
GATK

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