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First published online 11 April 2006
doi: 10.1242/jcs.02903

Journal of Cell Science 119, 1801-1811 (2006)
Published by The Company of Biologists 2006
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Research Article

Dynamic microtubules regulate the local concentration of E-cadherin at cell-cell contacts

Samantha J. Stehbens1,*, Andrew D. Paterson1,2,*, Matthew S. Crampton1, Annette M. Shewan1, Charles Ferguson1,3, Anna Akhmanova4, Robert G. Parton1,3 and Alpha S. Yap1,{ddagger}

1 Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia
2 School for Biomedical Science, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia
3 Centre for Microscopy and Microanalysis, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia
4 MGC Department of Cell Biology and Genetics, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands

{ddagger} Author for correspondence (e-mail: a.yap{at}imb.uq.edu.au)

Accepted 24 January 2006

In contrast to the well-established relationship between cadherins and the actin cytoskeleton, the potential link between cadherins and microtubules (MTs) has been less extensively investigated. We now identify a pool of MTs that extend radially into cell-cell contacts and are inhibited by manoeuvres that block the dynamic activity of MT plus-ends (e.g. in the presence of low concentrations of nocodazole and following expression of a CLIP-170 mutant). Blocking dynamic MTs perturbed the ability of cells to concentrate and accumulate E-cadherin at cell-cell contacts, as assessed both by quantitative immunofluorescence microscopy and fluorescence recovery after photobleaching (FRAP) analysis, but did not affect either transport of E-cadherin to the plasma membrane or the amount of E-cadherin expressed at the cell surface. This indicated that dynamic MTs allow cells to concentrate E-cadherin at cell-cell contacts by regulating the regional distribution of E-cadherin once it reaches the cell surface. Importantly, dynamic MTs were necessary for myosin II to accumulate and be activated at cadherin adhesive contacts, a mechanism that supports the focal accumulation of E-cadherin. We propose that this population of MTs represents a novel form of cadherin-MT cooperation, where cadherin adhesions recruit dynamic MTs that, in turn, support the local concentration of cadherin molecules by regulating myosin II activity at cell-cell contacts.

Key words: Cadherins, E-cadherin, Microtubules, Microtubule dynamics




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