The control of actin nucleotide exchange by thymosin beta 4 and profilin. A potential regulatory mechanism for actin polymerization in cells.
We present evidence for a new mechanism by which two major actin monomer binding proteins, thymosin beta 4 and profilin, may control the rate and the extent of actin polymerization in cells. Both proteins bind actin monomers transiently with a stoichiometry of 1:1. When bound to actin, thymosin beta 4 strongly inhibits the exchange of the nucleotide bound to actin by blocking its dissociation, while profilin catalytically promotes nucleotide exchange. Because both proteins exchange rapidly between actin molecules, low concentrations of profilin can overcome the inhibitory effects of high concentrations of thymosin beta 4 on the nucleotide exchange. These reactions may allow variations in profilin concentration (which may be regulated by membrane polyphosphoinositide metabolism) to control the ratio of ATP-actin to ADP-actin. Because ATP-actin subunits polymerize more readily than ADP-actin subunits, this ratio may play a key regulatory role in the assembly of cellular actin structures, particularly under circumstances of rapid filament turnover.
Goldschmidt-Clermont
P J
PJ
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Furman
M I
MI
Wachsstock
D
D
Safer
D
D
Nachmias
V T
VT
Pollard
T D
TD
D000199:Actins / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001667:Binding, Competitive; D001792:Blood Platelets / Q000378:metabolism; D003285:Contractile Proteins; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D051304:Profilins; D013947:Thymosin / Q000031:analogs & derivatives* / Q000378:metabolism; D000099201:Thymosin beta(4)
D000199:Actins; D000241:Adenosine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003285:Contractile Proteins; D008840:Microfilament Proteins; D010716:Phosphatidylinositols; D051304:Profilins; D013947:Thymosin; D000099201:Thymosin beta(4); C495738:PFN1 protein, human