Joanne M Leerberg1, Guillermo A Gomez1, Suzie Verma1, Elliott J Moussa1, Selwin K Wu1, Rashmi Priya1, Brenton D Hoffman2, Carsten Grashoff3, Martin A Schwartz4, Alpha S Yap5. 1. Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia 4072, Australia. 2. Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA. 3. Group of Molecular Mechanotransduction, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany. 4. Yale Cardiovascular Research Center and Departments of Cardiovascular Medicine, Cell Biology, and Biomedical Engineering, Yale University, New Haven, CT 06520, USA. 5. Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia 4072, Australia. Electronic address: a.yap@uq.edu.au.
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.
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: Adrienne K Barry; Hamid Tabdili; Ismaeel Muhamed; Jun Wu; Nitesh Shashikanth; Guillermo A Gomez; Alpha S Yap; Cara J Gottardi; Johan de Rooij; Ning Wang; Deborah E Leckband Journal: J Cell Sci Date: 2014-02-12 Impact factor: 5.285
Authors: Eva M Kovacs; Suzie Verma; Radiya G Ali; Aparna Ratheesh; Nicholas A Hamilton; Anna Akhmanova; Alpha S Yap Journal: Nat Cell Biol Date: 2011-07-24 Impact factor: 28.824
Authors: Adam C Martin; Michael Gelbart; Rodrigo Fernandez-Gonzalez; Matthias Kaschube; Eric F Wieschaus Journal: J Cell Biol Date: 2010-03-01 Impact factor: 10.539
Authors: Carsten Grashoff; Brenton D Hoffman; Michael D Brenner; Ruobo Zhou; Maddy Parsons; Michael T Yang; Mark A McLean; Stephen G Sligar; Christopher S Chen; Taekjip Ha; Martin A Schwartz Journal: Nature Date: 2010-07-08 Impact factor: 49.962
Authors: M Watabe-Uchida; N Uchida; Y Imamura; A Nagafuchi; K Fujimoto; T Uemura; S Vermeulen; F van Roy; E D Adamson; M Takeichi Journal: J Cell Biol Date: 1998-08-10 Impact factor: 10.539
Authors: Craig Furman; Alisha L Sieminski; Adam V Kwiatkowski; Douglas A Rubinson; Eliza Vasile; Roderick T Bronson; Reinhard Fässler; Frank B Gertler Journal: J Cell Biol Date: 2007-11-12 Impact factor: 10.539
Authors: Edouard Hannezo; Bo Dong; Pierre Recho; Jean-François Joanny; Shigeo Hayashi Journal: Proc Natl Acad Sci U S A Date: 2015-06-15 Impact factor: 11.205