Classical cadherin adhesion molecules are key determinants of cell–cell recognition during development and in post-embryonic life. A decisive step in productive cadherin-based recognition is the conversion of nascent adhesions into stable zones of contact. It is increasingly clear that such contact zone extension entails active cooperation between cadherin adhesion and the force-generating capacity of the actin cytoskeleton. Cortactin has recently emerged as an important regulator of actin dynamics in several forms of cell motility. We now report that cortactin is recruited to cell–cell adhesive contacts in response to homophilic cadherin ligation. Notably, cortactin accumulates preferentially, with Arp2/3, at cell margins where adhesive contacts are being extended. Recruitment of cortactin is accompanied by a ligation-dependent biochemical interaction between cortactin and the cadherin adhesive complex. Inhibition of cortactin activity in cells blocked Arp2/3-dependent actin assembly at cadherin adhesive contacts, significantly reduced cadherin adhesive contact zone extension, and perturbed both cell morphology and junctional accumulation of cadherins in polarized epithelia. Together, our findings identify a necessary role for cortactin in the cadherin–actin cooperation that supports productive contact formation.
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15 March 2004
Article|
March 15 2004
Cortactin is necessary for E-cadherin–mediated contact formation and actin reorganization
Falak M. Helwani,
Falak M. Helwani
1Division of Molecular Cell Biology, Institute for Molecular Bioscience
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Eva M. Kovacs,
Eva M. Kovacs
2School of Biomedical Science, University of Queensland, Brisbane, Queensland 4072, Australia
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Andrew D. Paterson,
Andrew D. Paterson
2School of Biomedical Science, University of Queensland, Brisbane, Queensland 4072, Australia
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Suzie Verma,
Suzie Verma
1Division of Molecular Cell Biology, Institute for Molecular Bioscience
2School of Biomedical Science, University of Queensland, Brisbane, Queensland 4072, Australia
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Radiya G. Ali,
Radiya G. Ali
2School of Biomedical Science, University of Queensland, Brisbane, Queensland 4072, Australia
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Alan S. Fanning,
Alan S. Fanning
3Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
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Scott A. Weed,
Scott A. Weed
4Department of Craniofacial Biology, University of Colorado Health Sciences Center, Denver, CO 80262
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Alpha S. Yap
Alpha S. Yap
1Division of Molecular Cell Biology, Institute for Molecular Bioscience
2School of Biomedical Science, University of Queensland, Brisbane, Queensland 4072, Australia
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Falak M. Helwani
1Division of Molecular Cell Biology, Institute for Molecular Bioscience
Eva M. Kovacs
2School of Biomedical Science, University of Queensland, Brisbane, Queensland 4072, Australia
Andrew D. Paterson
2School of Biomedical Science, University of Queensland, Brisbane, Queensland 4072, Australia
Suzie Verma
1Division of Molecular Cell Biology, Institute for Molecular Bioscience
2School of Biomedical Science, University of Queensland, Brisbane, Queensland 4072, Australia
Radiya G. Ali
2School of Biomedical Science, University of Queensland, Brisbane, Queensland 4072, Australia
Alan S. Fanning
3Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
Scott A. Weed
4Department of Craniofacial Biology, University of Colorado Health Sciences Center, Denver, CO 80262
Alpha S. Yap
1Division of Molecular Cell Biology, Institute for Molecular Bioscience
2School of Biomedical Science, University of Queensland, Brisbane, Queensland 4072, Australia
Address correspondence to Alpha S. Yap, Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia. Tel.: 61-7-3346-2013. Fax: 61-7-3346-2101. email: [email protected]
F.M. Helwani and E.M. Kovacs contributed equally to this paper.
The online version of this article includes supplemental material.
Abbreviations used in this paper: hE-CHO, CHO cell stably transfected with human E-cadherin; hE/Fc, human E-cadherin fused to the Fc region of IgG; NTA, NH2-terminal acidic; RNAi, RNA interference; TIRF, total internal reflection fluorescence.
Received:
September 05 2003
Accepted:
January 15 2004
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2004
J Cell Biol (2004) 164 (6): 899–910.
Article history
Received:
September 05 2003
Accepted:
January 15 2004
Citation
Falak M. Helwani, Eva M. Kovacs, Andrew D. Paterson, Suzie Verma, Radiya G. Ali, Alan S. Fanning, Scott A. Weed, Alpha S. Yap; Cortactin is necessary for E-cadherin–mediated contact formation and actin reorganization . J Cell Biol 15 March 2004; 164 (6): 899–910. doi: https://doi.org/10.1083/jcb.200309034
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