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Cortactin: coupling membrane dynamics to cortical actin assembly

Oncogene volume 20, pages 6418–6434 (2001)Cite this article

Abstract

Exposure of cells to a variety of external signals causes rapid changes in plasma membrane morphology. Plasma membrane dynamics, including membrane ruffle and microspike formation, fusion or fission of intracellular vesicles, and the spatial organization of transmembrane proteins, is directly controlled by the dynamic reorganization of the underlying actin cytoskeleton. Two members of the Rho family of small GTPases, Cdc42 and Rac, have been well established as mediators of extracellular signaling events that impact cortical actin organization. Actin-based signaling through Cdc42 and Rac ultimately results in activation of the actin-related protein (Arp) 2/3 complex, which promotes the formation of branched actin networks. In addition, the activity of both receptor and non-receptor protein tyrosine kinases along with numerous actin binding proteins works in concert with Arp2/3-mediated actin polymerization in regulating the formation of dynamic cortical actin-associated structures. In this review we discuss the structure and role of the cortical actin binding protein cortactin in Rho GTPase and tyrosine kinase signaling events, with the emphasis on the roles cortactin plays in tyrosine phosphorylation-based signal transduction, regulating cortical actin assembly, transmembrane receptor organization and membrane dynamics. We also consider how aberrant regulation of cortactin levels contributes to tumor cell invasion and metastasis.

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Acknowledgements

We wish to thank Drs Helene Marquis and Steve Anderson (University of Colorado Health Sciences Center) for providing Listeria infected and v-Src transformed cells, Dr Alan Fanning (Yale University) for helpful discussions and Julie Head for technical support. JT Parsons acknowledges the support of NIH grants CA40042 and CA29243. SA Weed is a member of the University of Colorado Cancer Center.

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  1. Department of Craniofacial Biology, University of Colorado Health Sciences Center, Denver, CO 80262, Colorado, USA

    Scott A Weed

  2. Department of Microbiology, Health Sciences Center, University of Virginia, Charlottesville, VA 22903, Virginia, USA

    J Thomas Parsons

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Correspondence to Scott A Weed.

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Weed, S., Parsons, J. Cortactin: coupling membrane dynamics to cortical actin assembly. Oncogene 20, 6418–6434 (2001). https://doi.org/10.1038/sj.onc.1204783

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