Which proteins are involved in actin bundling and filopodia formation and function?
['CRP1, a protein localized in filopodia of growth cones, is involved in dendritic growth', 'CRP1, which cross-links actin filaments to make actin bundles, is the only CRP family member expressed in the CNS with little known about its function in nerve cells.', 'Here, we report that CRP1 colocalizes with actin in the filopodia of growth cones in cultured rat hippocampal neurons.', 'Knockdown of CRP1 expression by short hairpin RNA interference results in inhibition of filopodia formation and dendritic growth in neurons.', 'Overexpression of CRP1 increases filopodia formation and neurite branching, which require its actin-bundling activity.', 'F-ascin is an actin-bundling protein involved in filopodia assembly and cancer invasion and metastasis of multiple epithelial cancer types.', 'In this study, we investigated the role of fascin, a cytoskeleton actin-bundling protein involved in the formation of filopodia and cell migration, in prostate cancer progression.', 'In cellular models, fascin gene silencing using small interfering RNA in the androgen-independent prostate cancer cell line DU145 decreased cell motility and invasiveness while increasing cell adhesive properties.', 'Fascin is an actin-bundling protein that induces membrane protrusions and cell motility after the formation of lamellipodia or filopodia.', 'The PCH family member MAYP/PSTPIP2 directly regulates F-actin bundling and enhances filopodia formation and motility in macrophages', 'Overexpression of MAYP decreased CSF-1-induced membrane ruffling and increased filopodia formation, motility and CSF-1-mediated chemotaxis.', 'The opposite phenotype was observed with reduced expression of MAYP, indicating that MAYP is a negative regulator of CSF-1-induced membrane ruffling and positively regulates formation of filopodia and directional migration.', 'Overexpression of MAYP led to a reduction in total macrophage F-actin content but was associated with increased actin bundling. Consistent with this, purified MAYP bundled F-actin and regulated its turnover in vitro.', 'In addition, MAYP colocalized with cortical and filopodial F-actin in vivo.', 'Because filopodia are postulated to increase directional motility by acting as environmental sensors, the MAYP-stimulated increase in directional movement may be at least partly explained by enhancement of filopodia formation.', 'We report an unexpected direct association between fascin, an actin-bundling component of filopodia, microspikes and lamellipodial ribs, and protein kinase Calpha (PKCalpha), a regulator of focal adhesions.', 'Fascin is an actin-bundling protein involved in filopodia assembly and cancer invasion and metastasis of multiple epithelial cancer types.', 'Actin-crosslinking proteins organize actin into highly dynamic and architecturally diverse subcellular scaffolds that orchestrate a variety of mechanical processes, including lamellipodial and filopodial protrusions in motile cells.', 'IRSp53, a multi-domain protein that can associate with the Rho-GTPases Rac and Cdc42, participates in these processes mainly through its amino-terminal IMD (IRSp53 and MIM domain). The isolated IMD has actin-bundling activity in vitro and is sufficient to induce filopodia in vivo.', 'Eps8 activates and synergizes with IRSp53 in mediating actin bundling in vitro, enhancing IRSp53-dependent membrane extensions in vivo.', 'Consistently, Cdc42-induced filopodia are inhibited following individual removal of either IRSp53 or Eps8.', 'Collectively, these results support a model whereby the synergic bundling activity of the IRSp53-Eps8 complex, regulated by Cdc42, contributes to the generation of actin bundles, thus promoting filopodial protrusions.', 'The bundling activity of vasodilator-stimulated phosphoprotein is required for filopodium formation', 'Filopodia are highly dynamic finger-like cell protrusions filled with parallel bundles of actin filaments. Previously we have shown that Diaphanous-related formin dDia2 is involved in the formation of filopodia. Another key player for the formation of filopodia across many species is vasodilator-stimulated phosphoprotein (VASP).', 'It has been proposed that the essential role of VASP for formation of filopodia is its competition with capping proteins for filament barbed-end interaction.', 'Only WT DdVASP, but not a mutant lacking the F-actin bundling activity, could rescue the ability of these cells to form WT-like filopodia.', 'Our data suggest that DdVASP is complexed with dDia2 in filopodial tips and support formin-mediated filament elongation by bundling nascent actin filaments.', 'Insulin receptor tyrosine kinase substrate p53 (IRSp53) has been identified as an SH3 domain-containing adaptor that links Rac1 with a Wiskott-Aldrich syndrome family verprolin-homologous protein 2 (WAVE2) to induce lamellipodia or Cdc42 with Mena to induce filopodia.', 'Here, we show that the N-terminal predicted helical stretch of 250 amino acids of IRSp53 is an evolutionarily conserved F-actin bundling domain involved in filopodium formation.', 'The IMD alone, derived from either IRSp53 or MIM, induced filopodia in HeLa cells and the formation of tightly packed parallel F-actin bundles in vitro.', 'These results suggest that IRSp53 and MIM belong to a novel actin bundling protein family.', 'Role of the actin bundling protein fascin in growth cone morphogenesis: localization in filopodia and lamellipodia', 'Fascin localized to radially oriented actin bundles in lamellipodia (ribs) and filopodia.', 'Using a fascin antibody and a GFP fascin construct, we found that fascin incorporated into actin bundles from the beginning of growth cone formation at the cut end of axons.', 'Later, during growth cone morphogenesis when actin ribs shortened, the proximal fascin-free zone of bundles increased, but fascin was retained in the distal, filopodial portion of bundles.', 'Treatment with tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), which phosphorylates fascin and decreases its affinity for actin, resulted in loss of all actin bundles from growth cones.', 'Our findings suggest that fascin may be particularly important for the linear structure and dynamics of filopodia and for lamellipodial rib dynamics by regulating filament organization in bundles.']
['A number of proteins have been found to regulate F-actin bundling and enhance filopodia formation and motility. Among these are Cysteine-rich protein 1 (CRP1), Fascin, Macrophage actin-associated tyrosine phosphorylated protein (MAYP/PSTPIP2), Insulin receptor tyrosine kinase substrate p53 (IRSp53), Missing in metastasis protein (MIM), Eps8, Diaphanous-related formin (dDia2) and Vasodilator-stimulated phosphoprotein (VASP).']
['Cysteine-rich protein 1 (CRP1)', 'Fascin', 'Macrophage actin-associated tyrosine phosphorylated protein (MAYP/PSTPIP2)', 'Insulin receptor tyrosine kinase substrate p53 (IRSp53)', 'Missing in metastasis protein (MIM)', 'Eps8', 'Diaphanous-related formin (dDia2)', 'Vasodilator-stimulated phosphoprotein (VASP)']