Functional Modules

    Capping protein is involved in actin filament assembly and disassembly[Edit]

    Capping proteins control access to the free barbed ends of actin filaments and is therefore a major factor affecting actin filament elongation. Capping proteins have a high affinity for barbed ends and their micromolar concentration in the cytoplasm ensures that most barbed ends are capped [1, 2]. Depletion of capping protein promotes increased filament assembly away from the leading edge in migrating cells [3]. In vitro experiments reveal that this results in a significant loss of lamellipodia yet a sharp increase in filopodia formation [3]. 

    In the case of filopodia formation, the barbed end of a filament can only be extended if the ends of the filament
    fluctuate away from the membrane to allow the incorporation of new actin monomers; when this occurs, the free barbed ends may become bound by heterodimeric capping proteins [1, 2]. Capping proteins are concentrated at the leading edge where they help to modulate the monomeric G-actin pool and to control the density and length of actin filaments [4, 5] (reviewed in [6]).

    Capping proteins (aka β-actinin, CapZ or Cap32/34) help favor actin assembly by preventing the loss of actin subunits to the barbed end (reviewed in [5]). The Ena/VASP protein family accumulates at the plasma membrane to antagonize barbed end capping proteins and to enable actin polymerization into longer filaments [7, 8]. Other capping factors (e.g. gelsolin, cytochalasin) bind G-actin monomers and/or unstable oligomers and increase the rate of nucleation [9]. Capping protein activity is inhibited directly by phosphatidylinositol (4,5)-bisphosphate (PIP2), V-1 (aka myotrophin), or CARMIL [1, 10,11, 12] (reviewed in [5]).

    References

    1. Schafer DA., Jennings PB., Cooper JA. Dynamics of capping protein and actin assembly in vitro: uncapping barbed ends by polyphosphoinositides. J. Cell Biol. 1996; 135(1). [PMID: 8858171]
    2. Narita A., Takeda S., Yamashita A., Maéda Y. Structural basis of actin filament capping at the barbed-end: a cryo-electron microscopy study. EMBO J. 2006; 25(23). [PMID: 17110933]
    3. Mejillano MR., Kojima S., Applewhite DA., Gertler FB., Svitkina TM., Borisy GG. Lamellipodial versus filopodial mode of the actin nanomachinery: pivotal role of the filament barbed end. Cell 2004; 118(3). [PMID: 15294161]
    4. Lai FP., Szczodrak M., Block J., Faix J., Breitsprecher D., Mannherz HG., Stradal TE., Dunn GA., Small JV., Rottner K. Arp2/3 complex interactions and actin network turnover in lamellipodia. EMBO J. 2008; 27(7). [PMID: 18309290]
    5. Iwasa JH., Mullins RD. Spatial and temporal relationships between actin-filament nucleation, capping, and disassembly. Curr. Biol. 2007; 17(5). [PMID: 17331727]
    6. Wear MA., Cooper JA. Capping protein: new insights into mechanism and regulation. Trends Biochem. Sci. 2004; 29(8). [PMID: 15362226]
    7. 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]
    8. 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]
    9. Tellam R., Frieden C. Cytochalasin D and platelet gelsolin accelerate actin polymer formation. A model for regulation of the extent of actin polymer formation in vivo. Biochemistry 1982; 21(13). [PMID: 6285961]
    10. 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]
    11. Taoka M., Ichimura T., Wakamiya-Tsuruta A., Kubota Y., Araki T., Obinata T., Isobe T. V-1, a protein expressed transiently during murine cerebellar development, regulates actin polymerization via interaction with capping protein. J. Biol. Chem. 2003; 278(8). [PMID: 12488317]
    12. Yang C., Pring M., Wear MA., Huang M., Cooper JA., Svitkina TM., Zigmond SH. Mammalian CARMIL inhibits actin filament capping by capping protein. Dev. Cell 2005; 9(2). [PMID: 16054028]
    Updated on: Wed, 26 Feb 2014 10:53:18 GMT
    History