What is the role of profilin in formin-nucleated actin cable assembly?2018-02-06T11:22:57+00:00

What is the role of profilin in formin-nucleated actin cable assembly?

Profilin binds simultaneously to formin and actin monomers; this interaction tethers multiple profilin-actin complexes near the growing end of actin filaments, which promotes the processive addition of actin subunits [1][2]. Profilin uses the energy from ATP hydrolysis generated during actin polymerization to facilitate actin assembly [2]. Profilin binds to cytoplasmic ATP-actin monomers better than cytoplasmic ADP-actin monomers [3].

Profilin has been suggested to generally increase the elongation rate of formin-associated filaments by:

  • Catalyzing the exchange of ADP for ATP on actin monomers [4][5].
  • Blocking free monomers from elongating pointed ends [4].
  • Lowering the critical concentration at the barbed end [2].
  • Promoting the association of G-actin-ATP to the barbed end [6].

Importantly however, profilin also promotes disassembly of actin filaments by sequestering monomeric G-actin, thereby blocking its association with the barbed ends and promoting its disassembly from the pointed ends of actin filaments [4]. The combined actions of profilin and ADF/cofilin synergize to enhance turnover of actin filaments [7].

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References

  1. Watanabe N, Madaule P, Reid T, Ishizaki T, Watanabe G, Kakizuka A, Saito Y, Nakao K, Jockusch BM, and Narumiya S. p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin. EMBO J. 1997; 16(11):3044-56. [PMID: 9214622]
  2. Pantaloni D, and Carlier MF. How profilin promotes actin filament assembly in the presence of thymosin beta 4. Cell 1993; 75(5):1007-14. [PMID: 8252614]
  3. Perelroizen I, Didry D, Christensen H, Chua NH, and Carlier MF. Role of nucleotide exchange and hydrolysis in the function of profilin in action assembly. J. Biol. Chem. 1996; 271(21):12302-9. [PMID: 8647830]
  4. Ressad F, Didry D, Egile C, Pantaloni D, and Carlier MF. Control of actin filament length and turnover by actin depolymerizing factor (ADF/cofilin) in the presence of capping proteins and ARP2/3 complex. J. Biol. Chem. 1999; 274(30):20970-6. [PMID: 10409644]
  5. Yarmola EG, Dranishnikov DA, and Bubb MR. Effect of profilin on actin critical concentration: a theoretical analysis. Biophys. J. 2008; 95(12):5544-73. [PMID: 18835900]
  6. Kang F, Purich DL, and Southwick FS. Profilin promotes barbed-end actin filament assembly without lowering the critical concentration. J. Biol. Chem. 1999; 274(52):36963-72. [PMID: 10601251]
  7. Didry D, Carlier MF, and Pantaloni D. Synergy between actin depolymerizing factor/cofilin and profilin in increasing actin filament turnover. J. Biol. Chem. 1998; 273(40):25602-11. [PMID: 9748225]