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    I-BAR and Other Proteins/Factors[Edit]

    Proteins containing I-BAR (inverted Bin/amphiphysin/Rvs i.e. IRSp53 Missing-in-metastasis homology Domain or IMD) cooperate with various components of actin filament assembly, to promote filopodia protrusion, via several mechanisms including the stimulation of F-actin crosslinking [1].

    A specific example of an I-BAR domain-containing actin crosslinker and scaffolding protein is IRSp53, which localizes to the tips of filopodia [2]. The activity of IRSp53 is enhanced by Cdc42 or Rac1 GTPases during filopodia formation [3, 4, 5]. Although this protein performs several functions and binds other actin regulators such as Mena (a Ena/VASP family protein [4]) and formin (e.g. mDia1 [6]), its role in F-actin binding and crosslinking is well established and has been attributed to its IMD domain [5, 7].

    Additional molecules contribute to the cross linking of actin filaments and these include fimbrin as well as lesser known actin crosslinking proteins such as Arg (Abl-related gene). This latter example is involved in lamellipodial protrusion, independent of its kinase activity, but concomitant with its microtubule binding activity [8].

    References

    1. Peter BJ., Kent HM., Mills IG., Vallis Y., Butler PJ., Evans PR., McMahon HT. BAR domains as sensors of membrane curvature: the amphiphysin BAR structure. Science 2004; 303(5657). [PMID: 14645856]
    2. Nakagawa H., Miki H., Nozumi M., Takenawa T., Miyamoto S., Wehland J., Small JV. IRSp53 is colocalised with WAVE2 at the tips of protruding lamellipodia and filopodia independently of Mena. J. Cell. Sci. 2003; 116(Pt 12). [PMID: 12734400]
    3. Govind S., Kozma R., Monfries C., Lim L., Ahmed S. Cdc42Hs facilitates cytoskeletal reorganization and neurite outgrowth by localizing the 58-kD insulin receptor substrate to filamentous actin. J. Cell Biol. 2001; 152(3). [PMID: 11157984]
    4. Krugmann S., Jordens I., Gevaert K., Driessens M., Vandekerckhove J., Hall A. Cdc42 induces filopodia by promoting the formation of an IRSp53:Mena complex. Curr. Biol. 2001; 11(21). [PMID: 11696321]
    5. Yamagishi A., Masuda M., Ohki T., Onishi H., Mochizuki N. A novel actin bundling/filopodium-forming domain conserved in insulin receptor tyrosine kinase substrate p53 and missing in metastasis protein. J. Biol. Chem. 2004; 279(15). [PMID: 14752106]
    6. Fujiwara T., Mammoto A., Kim Y., Takai Y. Rho small G-protein-dependent binding of mDia to an Src homology 3 domain-containing IRSp53/BAIAP2. Biochem. Biophys. Res. Commun. 2000; 271(3). [PMID: 10814512]
    7. Millard TH., Bompard G., Heung MY., Dafforn TR., Scott DJ., Machesky LM., Fütterer K. Structural basis of filopodia formation induced by the IRSp53/MIM homology domain of human IRSp53. EMBO J. 2005; 24(2). [PMID: 15635447]
    8. Miller AL., Wang Y., Mooseker MS., Koleske AJ. The Abl-related gene (Arg) requires its F-actin-microtubule cross-linking activity to regulate lamellipodial dynamics during fibroblast adhesion. J. Cell Biol. 2004; 165(3). [PMID: 15138293]
    Updated on: Mon, 20 Oct 2014 09:35:30 GMT
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