Cooperation between cadherins and the actin cytoskeleton controls many aspects of epithelial biogenesis. We report here that myosin VI critically regulates the morphogenesis of epithelial cell–cell contacts. As epithelial monolayers mature in culture, discontinuous cell–cell contacts are initially replaced by continuous (cohesive) contacts. Myosin VI is recruited to cell contacts as they become linear and cohesive, where it forms a biochemical complex with epithelial cadherin (E-cadherin). Myosin VI is necessary for strong cadherin adhesion, for cells to form cohesive linear contacts, and for the integrity of the apical junctional complex. We find that vinculin mediates this effect of myosin VI. Myosin VI is necessary for vinculin and E-cadherin to interact. A combination of gain and loss of function approaches identifies vinculin as a downstream effector of myosin VI that is necessary for the integrity of intercellular contacts. We propose that myosin VI and vinculin form a molecular apparatus that generates cohesive cell–cell contacts in cultured mammalian epithelia.
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30 July 2007
Article|
July 30 2007
Myosin VI and vinculin cooperate during the morphogenesis of cadherin cell–cell contacts in mammalian epithelial cells
Madhavi P. Maddugoda,
Madhavi P. Maddugoda
Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia
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Matthew S. Crampton,
Matthew S. Crampton
Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia
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Annette M. Shewan,
Annette M. Shewan
Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia
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Alpha S. Yap
Alpha S. Yap
Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia
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Madhavi P. Maddugoda
Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia
Matthew S. Crampton
Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia
Annette M. Shewan
Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia
Alpha S. Yap
Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia
Correspondence to Alpha S. Yap: [email protected]
Abbreviation used in this paper: DE-cadherin, Drosophila E-cadherin; E-cadherin, epithelial cadherin; F-actin, filamentous actin; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; KD, knockdown.
Received:
December 07 2006
Accepted:
July 03 2007
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2007
J Cell Biol (2007) 178 (3): 529–540.
Article history
Received:
December 07 2006
Accepted:
July 03 2007
Citation
Madhavi P. Maddugoda, Matthew S. Crampton, Annette M. Shewan, Alpha S. Yap; Myosin VI and vinculin cooperate during the morphogenesis of cadherin cell–cell contacts in mammalian epithelial cells . J Cell Biol 30 July 2007; 178 (3): 529–540. doi: https://doi.org/10.1083/jcb.200612042
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