Regulation of the neuronal actin cytoskeleton by ADF/cofilin

Abstract

Actin and microtubules are major cytoskeletal elements of most cells including neurons. In order for a cell to move and change shape, its cytoskeleton must undergo rearrangements that involve breaking down and reforming filaments. Many recent reviews have focused on the signaling pathways emanating from receptors that ultimately affect axon growth and growth cone steering. This particular review will address changes in the actin cytoskeleton modulated by the family of actin dynamizing proteins known as actin depolymerizing factor (ADF)/cofilin or AC proteins. Though much is known about inactivation of AC proteins through phosphorylation at ser3 by LIM or TES kinases, new mechanisms of regulation of AC have recently emerged. A novel phosphatase, slingshot (SSH), and the 14-3-3 family of regulatory proteins have also been found to affect AC activity. The potential role of AC proteins in modulating the actin organizational changes that accompany neurite initiation, axonogenesis, growth cone guidance, and dendritic spine formation will be discussed.

Sustained Arc/Arg3.1 Synthesis Controls Long-Term Potentiation Consolidation through Regulation of Local Actin Polymerization in the Dentate GyrusIn Vivo

“…One of the major cofilin kinases in neurons, Lim domain kinase (LIMK), is regulated by the Rho GTPase effectors Rho kinase (ROCK) and p21-activated kinase (PAK). Experiments showing normal LTP maintenance in the presence of ROCK inhibitors (A. Tiron and C. R. Bramham, unpublished observations) places emphasis on PAK, which both activates LIMK1 and inhibits activity of the cofilin phosphatase slingshot (Sarmiere and Bamburg, 2004). Furthermore, recent work shows that PAK and cofilin are phosphorylated in dendritic spines in response to LTP-inducing stimulation and application of BDNF Rex et al, 2007).…”

“…Cofilin is a member of a highly conserved family of actin-associated proteins that enhance actin filament severing and increase the off rate of actin monomers (Sarmiere and Bamburg, 2004). Phosphorylation of cofilin on Ser-3 inhibits cofilin activity and promotes F-actin formation.…”

Actin Depolymerization Factor/Cofilin Activation Regulates Actin Polymerization and Tension Development in Canine Tracheal Smooth Muscle

“…Cofilin S3E competes with phosphorylated cofilin and ADF for localization to sites where they are activated (44). Cofilin S3E may also compete with endogenous ADF/cofilin for binding to the ADF/cofilin-specific phosphatase, Slingshot, thereby preventing the activation of endogenous ADF/cofilin (43).…”

ADF/cofilin family proteins control formation of oriented actin-filament bundles in the cell body to trigger fibroblast polarization

“…It is becoming clear that the ADF/cofilin (AC) family of proteins, which catalyze actin-filament severing and depolymerization in cells (reviewed by Moon and Drubin, 1995;Sarmiere and Bamburg, 2003;Zigmond, 2004), is necessary for cell migration (reviewed by Bamburg and Wiggan, 2002). AC proteins are also known regulators of cell polarity, both in yeast (Drees et al, 2001;Okada et al, 2006) and also in migrating cell types, both to sustain already established polarity (Dawe et al, 2003) and to trigger cell polarization (Helen R. Dawe.…”

“…ACs are regulated in cells by several mechanisms (reviewed by Moon and Drubin, 1995;Sarmiere and Bamburg, 2003;Zigmond, 2004). In chick fibroblasts, AC is at least regulated by phosphorylation on serine 3 by LIM kinase (Dawe et al, 2003), which inactivates AC.…”