Cortactin branches out: Roles in regulating protrusive actin dynamics

Abstract

Since its discovery in the early 1990's, cortactin has emerged as a key signaling protein in many cellular processes, including cell adhesion, migration, endocytosis, and tumor invasion. While the list of cellular functions influenced by cortactin grows, the ability of cortactin to interact with and alter the cortical actin network is central to its role in regulating these processes. Recently, several advances have been made in our understanding of the interaction between actin and cortactin, providing insight into how these two proteins work together to provide a framework for normal and altered cellular function. This review examines how regulation of cortactin through post-translational modifications and interactions with multiple binding partners elicits changes in cortical actin cytoskeletal organization, impacting the regulation and formation of actin-rich motility structures. Cell Motil. Cytoskeleton 65: 687-707, 2008. '

The Association of Cortactin with Profilin-1 Is Critical for Smooth Muscle Contraction

“…The upstream regulator of Pfn-1 is not well identified. Because cortactin has been implicated in actin cytoskeletal remodeling (13,14), we hypothesized that contractile stimulation may promote the association of cortactin with Pfn-1, which may activate Pfn-1 in smooth muscle in response to contractile activation. To test this, HASM cells were stimulated with ACh (a stimulus implicated in airway tone and asthma) (38) for 5 min, or cells were unstimulated.…”

“…Cortactin is an adapter protein that is able to regulate actin filament assembly and branching in in vitro studies as well as adhesion, migration, and endocytosis of nonmuscle cells (13,14). Cortactin undergoes phosphorylation on Tyr-421 in fibroblasts during cell migration, and this has been implicated in the activation of cortactin (14).…”

“…Cortactin undergoes phosphorylation on Tyr-421 in fibroblasts during cell migration, and this has been implicated in the activation of cortactin (14). Cortactin may regulate actin polymerization by affecting the functional state of neuronal Wiskott-Aldrich syndrome protein, the Arp2/3 complex, and Nck in nonmuscle cells such as mouse embryonic fibroblasts and mouse 3T3 cells (13,15). However, the interaction of cortactin with Pfn-1 has not been explored.…”

Connexins, cell motility, and the cytoskeleton

“…Cortactin is a multi-domain protein that has been shown to play essential roles in many actin-based cellular processes, encompassing cell migration and invasion, axon guidance, neuronal morphogenesis, and tumor cell metastasis [reviewed by Ammer and Weed, 2008]. Its association with Cx43 has been shown by co-immunoprecipitation and co-localization in murine C2C12 myoblasts.…”

Cortactin gene amplification and expression in breast cancer: a chromogenic in situ hybridisation and immunohistochemical study

“…CTTN has been shown to play a critical role in various actin-mediated processes such as cell migration, adhesion and receptor mediated endocytosis [2,4]. 11q13 amplification is found in up to 15% of breast cancers [5][6][7][8] and has been suggested to be associated with oestrogen receptor (ER)-positive disease [9][10][11], lobular histological type [11,12], and poor prognosis [11,[13][14][15][16].…”