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

Nat Commun. 2018 Jul 19;9(1):2815. doi: 10.1038/s41467-018-05043-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actin Cytoskeleton / ultrastructure
  • Animals
  • Cell Polarity
  • Embryo, Mammalian
  • Female
  • Gene Expression Regulation, Developmental
  • Ion Transport
  • Mice, Knockout
  • Morphogenesis / genetics*
  • Muscle, Smooth / cytology
  • Muscle, Smooth / metabolism*
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / metabolism*
  • Phosphorylation
  • Polymerization
  • Potassium Channels, Inwardly Rectifying / deficiency
  • Potassium Channels, Inwardly Rectifying / genetics*
  • Proto-Oncogene Proteins c-akt / genetics*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Trachea / cytology
  • Trachea / growth & development
  • Trachea / metabolism*

Substances

  • Kir7.1 channel
  • Potassium Channels, Inwardly Rectifying
  • Proto-Oncogene Proteins c-akt