Solo and Keratin Filaments Regulate Epithelial Tubule Morphology

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  • Nishimura Ryosuke
    Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University Department of Cell Biology, Graduate School of Medical Sciences, Tokushima University
  • Kato Kagayaki
    Bioimage Informatics Group, Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences (NINS) Department of Imaging Science, Center for Novel Science Initiatives (CNSI), National Institutes of Natural Sciences (NINS) Division of Evolutionary Biology Biodiversity, National Institute for Basic Biology (NIBB)
  • Fujiwara Sachiko
    Division of Bioengineering, Graduate School of Engineering Science, Osaka University
  • Ohashi Kazumasa
    Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University
  • Mizuno Kensaku
    Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University

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<p>Epithelial tubules, consisting of the epithelial cell sheet with a central lumen, are the basic structure of many organs. Mechanical forces play an important role in epithelial tubulogenesis; however, little is known about the mechanisms controlling the mechanical forces during epithelial tubule morphogenesis. Solo (also known as ARHGEF40) is a RhoA-targeting guanine-nucleotide exchange factor that is involved in mechanical force-induced RhoA activation and stress fiber formation. Solo binds to keratin-8/keratin-18 (K8/K18) filaments, and this interaction plays a crucial role in mechanotransduction. In this study, we examined the roles of Solo and K8/K18 filaments in epithelial tubulogenesis using MDCK cells cultured in 3D collagen gels. Knockdown of either Solo or K18 resulted in rounder tubules with increased lumen size, indicating that Solo and K8/K18 filaments play critical roles in forming the elongated morphology of epithelial tubules. Moreover, knockdown of Solo or K18 decreased the level of diphosphorylated myosin light chain (a marker of contractile force) at the luminal and outer surfaces of tubules, suggesting that Solo and K8/K18 filaments are involved in the generation of the myosin II-mediated contractile force during epithelial tubule morphogenesis. In addition, K18 filaments were normally oriented along the long axis of the tubule, but knockdown of Solo perturbed their orientation. These results suggest that Solo plays crucial roles in forming the elongated morphology of epithelial tubules and in regulating myosin II activity and K18 filament organization during epithelial tubule formation.</p><p>Key words: epithelial tubulogenesis, Solo, keratin, Rho-GEF, myosin</p>

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