Cortactin: coupling, membrane dynamics to cortical actin assembly

Exposure of cells to a variety of external signals causes rapid changes in plasma membrane morphology. Plasma membrane dynamics, including membrane ru ffle and microspike formation, fusion or fission of intracellular vesicles, and the spatial organization of transmembrane proteins, is directly contro lled by the dynamic reorganization of the underlying actin cytoskeleton. Tw o members of the Rho family of small GTPases, Cdc42 and Rac, have been well established as mediators of extracellular signaling events that impact cor tical actin organization. Actin-based signaling through Cdc42 and Rac ultim ately 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 w ith numerous actin binding proteins works in concert with Arp2/3-mediated a ctin polymerization in regulating the formation of dynamic cortical actin-a ssociated structures. In this review we discuss the structure and role of t he cortical actin binding protein cortactin in Rho GTPase and tyrosine kina se signaling events, with the emphasis on the roles cortactin plays in tyro sine phosphorylation-based signal transduction, regulating cortical actin a ssembly, transmembrane receptor organization and membrane dynamics. We also consider how aberrant regulation of cortactin levels contributes to tumor cell invasion and metastasis.