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

• Published in: Nature communications 2018-07, Vol.9 (1), p.2815-13, Article 2815
• Main Authors: Yin, Wenguang, Kim, Hyun-Taek, Wang, ShengPeng, Gunawan, Felix, Wang, Lei, Kishimoto, Keishi, Zhong, Hua, Roman, Dany, Preussner, Jens, Guenther, Stefan, Graef, Viola, Buettner, Carmen, Grohmann, Beate, Looso, Mario, Morimoto, Mitsuru, Mardon, Graeme, Offermanns, Stefan, Stainier, Didier Y. R.
• Format: Article
• Language: English
• Subjects: 14/1; 14/19; 38/70; 38/77; 45; 45/23; 631/136/1660; 631/80/128; 64/60; 82/51; 82/80; Actin; Actin Cytoskeleton - metabolism; Actin Cytoskeleton - ultrastructure; AKT protein; Animals; Cell Polarity; Cytoskeleton; Embryo, Mammalian; Female; Gas exchange; Gene Expression Regulation, Developmental; Genetic screening; Homeostasis; Humanities and Social Sciences; Ion Transport; Lungs; Mice, Knockout; Molecular chains; Molecular modelling; Morphogenesis - genetics; multidisciplinary; Muscle, Smooth - cytology; Muscle, Smooth - metabolism; Muscles; Mutants; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - metabolism; Organs; Pharmacology; Phenotypes; Phosphorylation; Polarity; Polymerization; Potassium; Potassium Channels, Inwardly Rectifying - deficiency; Potassium Channels, Inwardly Rectifying - genetics; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Regulators; Science; Science (multidisciplinary); Signal Transduction; Smooth muscle; Trachea; Trachea - cytology; Trachea - growth & development; Trachea - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-05043-5

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. Tubulogenesis is required for the formation of many internal structures including the trachea. Here, the authors show that the potassium channel KCNJ13 regulates tracheal tube formation, with shorter tracheas forming in mutant mice due in part to changes in actin organization in tracheal smooth muscle cells.