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    How do formins facilitate filament polymerization?[Edit]

    Figure 1. Formin-mediated nucleation of actin filaments: The FH2 domains of the formin dimer (shown in green) bind to actin monomers to initiate filament assembly. Recent studies indicate this is assisted, or even mediated, by additional factors such as APC. The FH1 domains of the formin dimer (shown as black lines) have short polyproline sequences that interact with profilin. Profilin binds to both formin and actin monomers to increase the addition of actin monomers to the barbed end of the filament.
    Although a consensus has yet to be reached for the mechanism of formin-mediated nucleation, it is now well-established that activated formins facilitate elongation as dimers and form a donut-shaped complex around terminal actin subunits, orientating themselves toward the (+) end of the actin filament [1]. Binding, which is facilitated by FH2 (formin homology 2) domains within the formin monomers removes capping protein from the end of the filament and prevents re-capping to allow continued growth of filaments or cross-linked bundles ([2], reviewed in [3]). 

    Next, each formin monomer binds and captures profilin units, which are themselves already bound to G-actin monomers. This interaction is mediated by multiple stretches of polyproline residues within the FH1 domain of formins [4]. This domain is known to range from 15-229 residues, consist of between 35% and 100% proline residues, and contain up to 16 profilin binding sites [5]. Profilin maintains a steady pool of actin monomers by promoting ADP to ATP nucleotide exchange on G-actin[6]. These monomers of ATP-G-actin are then added the growing actin filament. The coupling of formin with the growing end prevents capping and allows continued growth of the filaments [7].



    References

    1.  [Diagnosis of pancreatic insuloma]. Khirurgiia (Mosk) 1978; undefined(11). [PMID: 214622]
    2. Yang C., Czech L., Gerboth S., Kojima S., Scita G., Svitkina T. Novel roles of formin mDia2 in lamellipodia and filopodia formation in motile cells. PLoS Biol. 2007; 5(11). [PMID: 18044991]
    3. Chesarone MA., DuPage AG., Goode BL. Unleashing formins to remodel the actin and microtubule cytoskeletons. Nat. Rev. Mol. Cell Biol. 2010; 11(1). [PMID: 19997130]
    4. Paul AS., Paul A., Pollard TD., Pollard T. The role of the FH1 domain and profilin in formin-mediated actin-filament elongation and nucleation. Curr. Biol. 2008; 18(1). [PMID: 18160294]
    5.  Formin proteins: a domain-based approach. Trends Biochem. Sci. 2005; 30(6). [PMID: 15950879]
    6. Romero S., Le Clainche C., Didry D., Egile C., Pantaloni D., Carlier MF. Formin is a processive motor that requires profilin to accelerate actin assembly and associated ATP hydrolysis. Cell 2004; 119(3). [PMID: 15507212]
    7. Pring M., Evangelista M., Boone C., Yang C., Zigmond SH. Mechanism of formin-induced nucleation of actin filaments. Biochemistry 2003; 42(2). [PMID: 12525176]
    Updated on: Mon, 20 Oct 2014 09:40:46 GMT
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