title: Tension-sensitive actin assembly supports contractility at the epithelial zonula adherens.
abstract: BACKGROUND
  Actomyosin-based contractility acts on cadherin junctions to support tissue integrity and morphogenesis. The actomyosin apparatus of the epithelial zonula adherens (ZA) is built by coordinating junctional actin assembly with Myosin II activation. However, the physical interaction between Myosin and actin filaments that is necessary for contractility can induce actin filament turnover, potentially compromising the contractile apparatus itself.
  
  
  RESULTS
  We now identify tension-sensitive actin assembly as one cellular solution to this design paradox. We show that junctional actin assembly is maintained by contractility in established junctions and increases when contractility is stimulated. The underlying mechanism entails the tension-sensitive recruitment of vinculin to the ZA. Vinculin, in turn, directly recruits Mena/VASP proteins to support junctional actin assembly. By combining strategies that uncouple Mena/VASP from vinculin or ectopically target Mena/VASP to junctions, we show that tension-sensitive actin assembly is necessary for junctional integrity and effective contractility at the ZA.
  
  
  CONCLUSIONS
  We conclude that tension-sensitive regulation of actin assembly represents a mechanism for epithelial cells to resolve potential design contradictions that are inherent in the way that the junctional actomyosin system is assembled. This emphasizes that maintenance and regulation of the actin scaffolds themselves influence how cells generate contractile tension.
authors: Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia 4072, Australia.
authors: Joanne M
authors: JM
authors: Leerberg
authors: Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia 4072, Australia.
authors: Guillermo A
authors: GA
authors: Gomez
authors: Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia 4072, Australia.
authors: Suzie
authors: S
authors: Verma
authors: Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia 4072, Australia.
authors: Elliott J
authors: EJ
authors: Moussa
authors: Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia 4072, Australia.
authors: Selwin K
authors: SK
authors: Wu
authors: Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia 4072, Australia.
authors: Rashmi
authors: R
authors: Priya
authors: Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
authors: Brenton D
authors: BD
authors: Hoffman
authors: Group of Molecular Mechanotransduction, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors: Carsten
authors: C
authors: Grashoff
authors: Yale Cardiovascular Research Center and Departments of Cardiovascular Medicine, Cell Biology, and Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
authors: Martin A
authors: MA
authors: Schwartz
authors: Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia 4072, Australia. Electronic address: a.yap@uq.edu.au.
authors: Alpha S
authors: AS
authors: Yap
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000502:physiology*; D022005:Adherens Junctions / Q000378:metabolism*; D018938:Caco-2 Cells; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism; D024501:Nonmuscle Myosin Type IIB / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D003598:Cytoskeletal Proteins; D016596:Vinculin; D024507:Nonmuscle Myosin Type IIA; D024501:Nonmuscle Myosin Type IIB