Regulation of the assembly and expression of actin is of major importa
nce in diverse cellular functions such as motility and adhesion and in
defining cellular and tissue architecture. These biological processes
are controlled by changing the balance between polymerized (F) and so
luble (G) actin. Previous stud ies have indicated the existence of an
autoregulatory pathway that links the state of assembly and expression
of actin, resulting in the reduction of actin synthesis after actin f
ilaments are depolymerized. We have employed the marine toxins swinhol
ide A and latrunculin A, both disrupting the organization of the actin
-cytoskeleton, to determine whether this autoregulatory response is ac
tivated by a decrease in the level of polymerized actin or by an incre
ase in monomeric actin concentrations in the cell. We showed that in c
ells treated with swinholide A the level of filamentous actin is decre
ased, and using a reversible cross-linking reagent, we found that acti
n dimers are formed. Latrunculin A also disassembled actin filaments,
bur produced monomeric actin, followed by a reduction in actin and vin
culin expression, while swinholide A treatment elevated the synthesis
of these proteins. In cells treated with both latrunculin A and swinho
lide A, dimeric actin was formed, and actin and vinculin synthesis wer
e higher than in control cells. These results suggest that the substra
te that confers an autoregulated reduction in actin expression is mono
meric actin, and when its level is decreased by dimeric actin formatio
n, actin synthesis is increased. J. Cell. Biochem. 65:469-378. (C) 199
7 Wiley-Liss, Inc.