MODULATION OF THE INTERACTION BETWEEN G-ACTIN AND THYMOSIN-BETA-4 BY THE ATP ADP RATIO - POSSIBLE IMPLICATION IN THE REGULATION OF ACTIN DYNAMICS

The interaction of G-actin with thymosin beta4 (Tbeta4), the major G-a ctin-sequestering protein in motile and proliferating cells, has been analyzed in vitro. Tbeta4 is found to have a 50-fold higher affinity f or MgATP-actin than for MgADP-actin. These results imply that in resti ng platelets and neutrophils, actin is sequestered by Tbeta4 as MgATP- G-actin. Kinetic experiments and theoretical calculations demonstrate that this ATP/ADP dependence of Tbeta4 affinity for G-actin can genera te a mechanism of desequestration of G-actin by ADP, in the presence o f physiological concentrations of Tbeta4 (almost-equal-to 0.1 mM). The desequestration of G-actin by ADP is kinetically enhanced by profilin , which accelerates the dissociation of ATP from G-actin. Whether a lo cal drop in the ATP/ADP ratio can allow local, transient desequestrati on and polymerization of actin either close to the plasma membrane, fo llowing platelet or neutrophil stimulation, or behind the Listeria bac terium in the host cell, while the surrounding cytoplasm contains sequ estered ATP-G-actin, is an open issue raised by the present work.