title: Synergy between actin depolymerizing factor/cofilin and profilin in increasing actin filament turnover.
abstract: The mechanism of control of the steady state of actin assembly by actin depolymerizing factor (ADF)/cofilin and profilin has been investigated. Using Tbeta4 as an indicator of the concentration of ATP-G-actin, we show that ADF increases the concentration of ATP-G-actin at steady state. The measured higher concentration of ATP-G-actin is quantitatively consistent with the increase in treadmilling, caused by the large increase in the rate of depolymerization from the pointed ends induced by ADF (Carlier, M.-F. , Laurent, V., Santolini, J., Didry, D., Melki, R., Xia, G.-X., Hong, Y., Chua, N.-H., and Pantaloni, D. (1997) J. Cell Biol. 136, 1307-1322). Experiments demonstrate that profilin synergizes with ADF to further enhance the turnover of actin filaments up to a value 125-fold higher than in pure F-actin solutions. Profilin and ADF act at the two ends of filaments in a complementary fashion to increase the processivity of treadmilling. Using the capping protein CapZ, we show that ADF increases the number of filaments at steady state by 1. 3-fold, which cannot account for the 25-fold increase in turnover rate. Computer modeling of the combined actions of ADF and profilin on the dynamics of actin filaments using experimentally determined rate constants generates a distribution of the different actin species at steady state, which is in quantitative agreement with the data.
authors.affiliation: Dynamique du Cytosquelette, Laboratoire d'Enzymologie et Biochimie Structurales, CNRS, 91198 Gif-sur-Yvette, France.
authors.forename: D
authors.initials: D
authors.lastname: Didry
authors.forename: M F
authors.initials: MF
authors.lastname: Carlier
authors.forename: D
authors.initials: D
authors.lastname: Pantaloni
mesh_terms: D051339:Actin Depolymerizing Factors; D000199:Actins / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D017360:Arabidopsis / Q000737:chemistry; D029681:Arabidopsis Proteins; D051347:CapZ Actin Capping Protein; D002417:Cattle; D003198:Computer Simulation; D003285:Contractile Proteins; D005453:Fluorescence; D007700:Kinetics; D008840:Microfilament Proteins / Q000502:physiology*; D009124:Muscle Proteins / Q000502:physiology; D009711:Nucleotides / Q000378:metabolism; D051304:Profilins; D011485:Protein Binding; D011487:Protein Conformation; D011817:Rabbits
chemical_list: C022920:ATP-G-actin; D051339:Actin Depolymerizing Factors; D000199:Actins; D029681:Arabidopsis Proteins; D051347:CapZ Actin Capping Protein; D003285:Contractile Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D009711:Nucleotides; C495746:PRF1 protein, Arabidopsis; D051304:Profilins; D000255:Adenosine Triphosphate