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

  • 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.
Metadaten
Author:Wenguang YinORCiD, Hyun-Taek Kim, Shengpeng Wang, Felix GunawanORCiD, Lei Wang, Keishi KishimotoORCiD, Hua Zhong, Dany Roman, Jens PreussnerORCiDGND, Stefan GüntherORCiD, Viola Graef, Carmen Büttner, Beate Grohmann, Mario LoosoORCiDGND, Mitsuru MorimotoORCiD, Graeme Mardon, Stefan OffermannsORCiDGND, Didier StainierORCiD
URN:urn:nbn:de:hebis:30:3-468909
DOI:https://doi.org/10.1038/s41467-018-05043-5
ISSN:2041-1723
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/30022023
Parent Title (English):Nature Communications
Publisher:Nature Publishing Group UK
Place of publication:[London]
Document Type:Article
Language:English
Year of Completion:2018
Date of first Publication:2018/07/19
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/08/02
Tag:Cytoskeleton; Morphogenesis
Volume:9
Issue:1, Art. 2815
Page Number:13
First Page:1
Last Page:13
Note:
Rights and permissions: Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
HeBIS-PPN:435733168
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0