Coronin 2A regulates a subset of focal-adhesion-turnover events through the cofilin pathway

Abstract

Precise control of cell-matrix adhesion is necessary for cell migration to occur. Fibroblasts lacking paxillin (PXN) or focal adhesion kinase (FAK), two core focal-adhesion components, display aberrant adhesion and decreased cell motility in vitro. Embryos deficient in genes that encode these proteins also lack proper mesoderm formation leading to embryonic lethality (Ilic et al., 1995;Hagel et al., 2002). In many types of cancer cell, focal adhesion proteins display either modulated protein expression or inappropriate regulation. For example, FAK is overexpressed in many types of cancer cells and is responsible for hyperphosphorylation of other focal-adhesion proteins (Mitra and Schlaepfer, 2006). Conversely, targeted disruption of the FAK gene in breast cancer models show that FAK is required for carcinoma formation and metastasis (Lahlou et al., 2007). Other focal-adhesion proteins have altered expression profiles in cancer models as well. Recent data suggest that the EGF-induced switch from expression of tensin-3 to the expression of the anti-adhesive molecule cten leads to increased metastasis of mammary tumor cells (Katz et al., 2007). These observations indicate that proper focal-adhesion dynamics are crucial for morphogenesis and play a significant role in cancer progression.Coronins are highly conserved F-actin binding proteins that are important for cell motility and actin dynamics (de Hostos et al., 1993;Cai et al., 2007;Foger et al., 2006). Mammalian genomes contain at least six coronin genes that can be separated into three types: type I (coronin 1A, 1B and 1C), type II (coronin 2A and 2B), and type III (coronin 7, also known as POD) (Uetrecht and Bear, 2006). Each of the coronins displays different tissue expression patterns with at least one type I coronin and POD expressed in all tissues and cell types. Type II coronins show a more restricted expression pattern, with strong enrichment in tissues containing epithelial and neuronal cell types (Cai et al., 2005).The subcellular localization of each of the coronin types is also quite distinct. Type I coronins localize primarily to the lamellipodia and some vesicular structures (Cai et al., 2005;Rosentreter et al., 2007), type II coronins localize to stress fibers and focal adhesions (Nakamura et al., 1999), and POD localizes to the Golgi apparatus (Rybakin et al., 2004). Type I coronins have a clear role in regulating cell motility, whereas the function of type II coronins remains unknown. Type I coronins such as coronin 1B coordinately regulate Arp2/3 and cofilin activities in lamellipodia (Cai et al., 2007). Coronin 1B targets Arp2/3-containing branches and replaces Arp2/3 at branches, leading to network remodeling and disassembly (Cai et al., 2008). In addition, coronin 1B is required for proper targeting of Slingshot-1L, an activating phosphatase for the ADF/cofilin family of actin-binding proteins to the rear of lamellipodia (Cai et al., 2007). It is unclear whether type II coronins execute similar functions at other cellular locations.ADF/cofil...

Stretching Actin Filaments within Cells Enhances their Affinity for the Myosin II Motor Domain

“…This is again in line with the report from Tang and Ostap, who showed that GFP-fused myo1b, a rat myosin I, localized along the cell periphery but not along stress fibers [60]. Distinct intracellular localizations of members of the same family of actin binding proteins have been reported for calponin-homology proteins [79], coronin [80], tropomyosin [81] and talin [82]. Notably, distinct intracellular localizations along specific actin-containing structures were also observed with the GFP-fused, isolated ABDs of Dictyostelium α-actinin and filamin, both of which are calponin homology proteins [79].…”

Mechanotransduction and extracellular matrix homeostasis

“…Finally, actin filaments stabilize under tension, decreasing both spontaneous depolymerization rates 124 and reducing their sensitivity to severing by cofilin 125 . As actin scaffolds are essential for focal adhesion stability, this effect can also influence the lifetime of focal adhesions 126 .…”

The Switch-associated Protein 70 (SWAP-70) Bundles Actin Filaments and Contributes to the Regulation of F-actin Dynamics

“…Thus, a commonly used surrogate marker for cofilin activity in vivo is the generation of actin free barbed ends (46,55), although barbed ends might also arise from other mechanisms (45). Compared with WT cells, Swap-70 Ϫ/Ϫ BMMCs are impaired in reducing the number of actin free barbed ends upon SCF stimulation (Fig.…”