Fig. 6.

Latrunculin paradox.⁹⁾ The left panel depicts the scheme of kinetic modeling used for estimating time-dependent concentration changes of each G-actin species either free or bound to LatB, Tβ4 and/or profilin. G, L, T, and P represent G-actin, LatB, thymosin-β4 (Tβ4) and profilin, respectively. The simulation results (middle and right graphs) revealed the paradoxical effect of latrunculin B. The primary action of latrunculin B is to bind G-actin and inhibit actin polymerization. In experiments, slowdown of actin elongation by mDia1 and a ~30% F-actin decrease were observed in cells treated with low-dose LatB. The change in the balance between F- and G-actin leads to the paradoxical, several fold increase in free G-actin accompanied by saturation of the G-actin sequestering activities in the simulation. Adopted with permission from J. Cell Sci. 121, 3403–3412, Fig. 4B (2008).