Functional Modules

    Ena/VASP[Edit]

    Proteins of the Ena/VASP family contribute to cell movement, axon guidance, neural tube closure and shape change in vertebrate cells by modulating actin filament organization and dynamics; these effects are achieved in part by regulating the morphology and behavior of actin-based structures such as lamellipodia and filopodia (reviewed in [1]). Ena/VASP proteins also modulate actin dynamics at sites of cell-ECM and cell-cell interactions and they are concentrated to the proximal portion of phosphotyrosine-rich domains at the ends of F-actin stress fibers [2]

    Ena/VASP proteins promote actin filament elongation by tethering actin filaments to sites of active actin assembly [345]. Ena/VASP proteins recruit actin nucleation and initiation factors (e.g. Arp2/3 complexformins) and promote F-actin assembly through profilin-binding (reviewed in [6]). The rate of Ena/VASP assisted actin filament elongation is determined by the recruitment of G-actin. This will occur via a G-actin binding site (GAB) that lies within the EVH2 domain and shares close sequence homology to WASP homology 2 motifs [7]. Ena/VASP proteins are also thought to accumulate at the plasma membrane where they alter actin polymerization by antagonizing the barbed (+) end capping proteins, thereby enabling the incorporation of actin into longer filaments [34]; however, controversy over their exact mechanism still exists (reviewed in [1]). In addition, Ena/VASP may promote actin assembly by an unknown mechanism that is independent of initiation factors, however, this has not been demonstrated in intact cells [8]

    References

    1. Bear JE., Gertler FB. Ena/VASP: towards resolving a pointed controversy at the barbed end. J. Cell. Sci. 2009; 122(Pt 12). [PMID: 19494122]
    2. Gertler FB., Niebuhr K., Reinhard M., Wehland J., Soriano P. Mena, a relative of VASP and Drosophila Enabled, is implicated in the control of microfilament dynamics. Cell 1996; 87(2). [PMID: 8861907]
    3. Bear JE., Svitkina TM., Krause M., Schafer DA., Loureiro JJ., Strasser GA., Maly IV., Chaga OY., Cooper JA., Borisy GG., Gertler FB. Antagonism between Ena/VASP proteins and actin filament capping regulates fibroblast motility. Cell 2002; 109(4). [PMID: 12086607]
    4. Breitsprecher D., Kiesewetter AK., Linkner J., Urbanke C., Resch GP., Small JV., Faix J. Clustering of VASP actively drives processive, WH2 domain-mediated actin filament elongation. EMBO J. 2008; 27(22). [PMID: 18923426]
    5. Lebrand C., Dent EW., Strasser GA., Lanier LM., Krause M., Svitkina TM., Borisy GG., Gertler FB. Critical role of Ena/VASP proteins for filopodia formation in neurons and in function downstream of netrin-1. Neuron 2004; 42(1). [PMID: 15066263]
    6. Chesarone MA., Goode BL. Actin nucleation and elongation factors: mechanisms and interplay. Curr. Opin. Cell Biol. 2009; 21(1). [PMID: 19168341]
    7. Breitsprecher D., Kiesewetter AK., Linkner J., Vinzenz M., Stradal TE., Small JV., Curth U., Dickinson RB., Faix J. Molecular mechanism of Ena/VASP-mediated actin-filament elongation. EMBO J. 2011; 30(3). [PMID: 21217643]
    8. Fradelizi J., Noireaux V., Plastino J., Menichi B., Louvard D., Sykes C., Golsteyn RM., Friederich E. ActA and human zyxin harbour Arp2/3-independent actin-polymerization activity. Nat. Cell Biol. 2001; 3(8). [PMID: 11483954]
    Updated on: Wed, 26 Feb 2014 10:54:28 GMT