14-3-3 regulates actin dynamics by stabilizing phosphorylated cofilin
Curr Biol, 12 (19):
1704-10 (October 2002)Gohla, Antje Bokoch, Gary M GM39434/GM/NIGMS NIH HHS/United States
Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.
England Current biology : CB Curr Biol. 2002 Oct 1;12(19):1704-10..Abstract
The functionality of the actin cytoskeleton depends on a dynamic equilibrium
between filamentous and monomeric actin. Proteins of the ADF/cofilin
family are essential for the high rates of actin filament turnover
observed in motile cells through regulation of actin polymerization/depolymerization
cycles. Rho GTPases act through p21-activated kinase-1 (Pak-1) and
Rho kinase to inhibit cofilin activity via the LIM kinase (LIMK)-mediated
phosphorylation of cofilin on Ser3. We report the identification
of 14-3-3zeta as a novel phosphocofilin binding protein involved
in the maintenance of the cellular phosphocofilin pool. A Ser3 phosphocofilin
binding protein was purified from bovine brain and was identified
as 14-3-3zeta by mass spectrometry. The phosphorylation-dependent
interaction between cofilin and 14-3-3zeta was confirmed in pulldown
and coimmunoprecipitation experiments. Both Ser3 phosphorylation
and a 14-3-3 recognition motif in cofilin are necessary for 14-3-3
binding. The expression of 14-3-3zeta increases phosphocofilin levels,
and the coexpression of 14-3-3zeta with LIMK further elevates phosphocofilin
levels and potentiates LIMK-dependent effects on the actin cytoskeleton.
This potentiation of cofilin action appears to be a result of the
protection of phosphocofilin from phosphatase-mediated dephosphorylation
at Ser3 by bound 14-3-3zeta. Taken together, these results suggest
that 14-3-3zeta proteins may play a dynamic role in the regulation
of cellular actin structures through the maintenance of phosphocofilin
levels.