Goldschmidt-Clermont P J, Furman M I, Wachsstock D, Safer D, Nachmias V T, Pollard T D
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Mol Biol Cell. 1992 Sep;3(9):1015-24. doi: 10.1091/mbc.3.9.1015.
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.
我们提供了一种新机制的证据，通过该机制，两种主要的肌动蛋白单体结合蛋白，即胸腺素β4和前纤维蛋白，可能控制细胞中肌动蛋白聚合的速率和程度。这两种蛋白均以1:1的化学计量比与肌动蛋白单体瞬时结合。当与肌动蛋白结合时，胸腺素β4通过阻止其解离来强烈抑制与肌动蛋白结合的核苷酸的交换，而前纤维蛋白则催化促进核苷酸交换。由于这两种蛋白在肌动蛋白分子之间快速交换，低浓度的前纤维蛋白可以克服高浓度胸腺素β4对核苷酸交换的抑制作用。这些反应可能使前纤维蛋白浓度的变化（可能由膜多磷酸肌醇代谢调节）来控制ATP-肌动蛋白与ADP-肌动蛋白的比例。由于ATP-肌动蛋白亚基比ADP-肌动蛋白亚基更容易聚合，该比例可能在细胞肌动蛋白结构的组装中起关键调节作用，特别是在细丝快速周转的情况下。
