Appropriate tension sensitivity of α-catenin ensures rounding morphogenesis of epithelial spheroids

DOI DOI Web Site Web Site PubMed 参考文献76件 オープンアクセス
  • Nishimura Ryosuke
    Department of Cell Biology, Graduate School of Medical Sciences, Tokushima University
  • Kato Kagayaki
    Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences
  • Saida Misako
    Spectrography and Bioimaging Facility, National Institute for Basic Biology
  • Kamei Yasuhiro
    Spectrography and Bioimaging Facility, National Institute for Basic Biology Department of Basic Biology, School of Life Science, The Graduate University for Advanced Studies (SOKENDAI)
  • Takeda Masahiro
    Ultra High Precision Optics Technology Team/Advanced Manufacturing Support Team, RIKEN Center for Advanced Photonics, RIKEN
  • Miyoshi Hiromi
    Ultra High Precision Optics Technology Team/Advanced Manufacturing Support Team, RIKEN Center for Advanced Photonics, RIKEN Applied Mechanobiology Laboratory, Faculty of Systems Design, Tokyo Metropolitan University
  • Yamagata Yutaka
    Ultra High Precision Optics Technology Team/Advanced Manufacturing Support Team, RIKEN Center for Advanced Photonics, RIKEN
  • Amano Yu
    Department of Bioscience, Kwansei Gakuin University
  • Yonemura Shigenobu
    Department of Cell Biology, Graduate School of Medical Sciences, Tokushima University Ultrastructural Research Team, RIKEN Center for Biosystems Dynamics Research

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<p>The adherens junction (AJ) is an actin filament-anchoring junction. It plays a central role in epithelial morphogenesis through cadherin-based recognition and adhesion among cells. The stability and plasticity of AJs are required for the morphogenesis. An actin-binding α-catenin is an essential component of the cadherin-catenin complex and functions as a tension transducer that changes its conformation and induces AJ development in response to tension. Despite much progress in understanding molecular mechanisms of tension sensitivity of α-catenin, its significance on epithelial morphogenesis is still unknown. Here we show that the tension sensitivity of α-catenin is essential for epithelial cells to form round spheroids through proper multicellular rearrangement. Using a novel in vitro suspension culture model, we found that epithelial cells form round spheroids even from rectangular-shaped cell masses with high aspect ratios without using high tension and that increased tension sensitivity of α-catenin affected this morphogenesis. Analyses of AJ formation and cellular tracking during rounding morphogenesis showed cellular rearrangement, probably through AJ remodeling. The rearrangement occurs at the cell mass level, but not single-cell level. Hypersensitive α-catenin mutant-expressing cells did not show cellular rearrangement at the cell mass level, suggesting that the appropriate tension sensitivity of α-catenin is crucial for the coordinated round morphogenesis.</p><p>Key words: α-catenin, vinculin, adherens junction, morphogenesis, mechanotransduction</p>

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