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Published online
doi:10.1083/jcb.200612042
The Journal of Cell Biology, Vol. 178, No. 3, 529-540
The Rockefeller University Press, 0021-9525 $30.00
© Maddugoda et al.
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Article

Myosin VI and vinculin cooperate during the morphogenesis of cadherin cell–cell contacts in mammalian epithelial cells



Madhavi P. Maddugoda, Matthew S. Crampton, Annette M. Shewan, and 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: a.yap{at}imb.uq.edu.au

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.

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.


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