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 beta 4 (T beta 4), the major G-actin-sequestering protein in motile and proliferating cells, has been analyzed in vitro. T beta 4 is found to have a 50-fold higher affinity for MgATP-actin than for MgADP-actin. These results imply that in resting platelets and neutrophils, actin is sequestered by T beta 4 as MgATP-G-actin. Kinetic experiments and theoretical calculations demonstrate that this ATP/ADP dependence of T beta 4 affinity for G-actin can generate a mechanism of desequestration of G-actin by ADP, in the presence of physiological concentrations of T beta 4 (approximately 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 local drop in the ATP/ADP ratio can allow local, transient desequestration and polymerization of actin either close to the plasma membrane, following platelet or neutrophil stimulation, or behind the Listeria bacterium in the host cell, while the surrounding cytoplasm contains sequestered ATP-G-actin, is an open issue raised by the present work.
Laboratoire d'Enzymologie, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
M F
MF
Carlier
C
C
Jean
K J
KJ
Rieger
M
M
Lenfant
D
D
Pantaloni
D000199:Actins / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002455:Cell Division; D003285:Contractile Proteins / Q000494:pharmacology; D007700:Kinetics; D008433:Mathematics; D008840:Microfilament Proteins / Q000302:isolation & purification / Q000494:pharmacology; D008954:Models, Biological; D009132:Muscles / Q000378:metabolism; D051304:Profilins; D012756:Sheep; D013154:Spleen / Q000378:metabolism; D013947:Thymosin / Q000378:metabolism*; D000099201:Thymosin beta(4)
D000199:Actins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003285:Contractile Proteins; D008840:Microfilament Proteins; D051304:Profilins; D013947:Thymosin; D000099201:Thymosin beta(4)