D. Didry et al., SYNERGY BETWEEN ACTIN DEPOLYMERIZING FACTOR COFILIN AND PROFILIN IN INCREASING ACTIN FILAMENT TURNOVER, The Journal of biological chemistry, 273(40), 1998, pp. 25602-25611
The mechanism of control of the steady state of actin assembly by acti
n depolymerizing factor (ADF)/cofilin and profilin has been investigat
ed. Using TP, as an indicator of the concentration of ATP-G-actin, we
show that ADF increases the concentration of ATP-G-actin at steady sta
te. The measured higher concentration of ATP-G-actin is quantitatively
consistent with the increase in treadmilling, caused by the large inc
rease 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 synergize
s 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 increa
se the processivity of treadmilling. Using the capping protein CapZ, w
e 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 rat
e. Computer modeling of the combined actions of ADF and profilin on th
e dynamics of actin filaments using experimentally determined rate con
stants generates a distribution of the different actin species at stea
dy state, which is in quantitative agreement with the data.