Cofilin takes the lead

Abstract

Cofilin has emerged as a key regulator of actin dynamics at the leading edge of motile cells. Through its actinsevering activity, it creates new actin barbed ends for polymerization and also depolymerizes old actin filaments. Its function is tightly regulated in the cell. Spatially, its activity is restricted by other actin-binding proteins, such as tropomyosin, which compete for accessibility of actin filament populations in different regions of the cell. At the molecular level, it is regulated by phosphorylation, pH and phosphatidylinositol (4,5)-bisphosphate binding downstream of signaling cascades. In addition, it also appears to be regulated by interactions with 14-3-3ζ and cyclase-associated protein. In vivo, cofilin acts synergistically with the Arp2/3 complex to amplify local actin polymerization responses upon cell stimulation, which gives it a central role in setting the direction of motility in crawling cells.

Actin Dynamics Regulated by the Balance of Neuronal Wiskott-Aldrich Syndrome Protein (N-WASP) and Cofilin Activities Determines the Biphasic Response of Glucose-induced Insulin Secretion

“…It has been shown that activated PAK1 phosphorylates LIMK1 (46) and that phosphorylated LIMK1 phosphorylates cofilin (i.e. inactivates cofilin), which decreases its actin depolymerizing activity (47,48). In addition, we found that phosphorylations of LIMK1 and cofilin are induced by glucose stimulation in MIN6-K8 ␤-cells.…”

“…PAK1 activates LIM kinase 1 (LIMK1) by its phosphorylation (46), which phosphorylates cofilin at serine 3. Phosphorylation of cofilin (inactive form) inhibits its actin depolymerizing activity by binding to actin monomers (47,48). Dephosphorylated cofilin (active form) increases the rate of actin depolymerization and maintains a pool of actin monomer (33).…”

Protein Kinase D Controls Actin Polymerization and Cell Motility through Phosphorylation of Cortactin

“…downstream of RhoA, during different stages of cell migration is necessary to finetune actin reorganization and polymerization events, providing the basis for altering cell motility. As proposed previously (8,9), cofilin has important functions in controlling the initial directional response of cells after sensing a chemotactic gradient. Cofilin severs old filaments replenishing the G-actin pool of cells and it generates new "free barbed ends" after being recruited to the active polymerization zone at what will become the leading edge of cells oriented toward a growth factor gradient (7).…”

“…By severing actin filaments, cofilin increases both the availability of G-actin monomers as well as the number of "barbed ends" for polymerization (7). Furthermore, severed filaments are the preferred substrate for dendritic nucleation by the Arp complex (8,9). Localized induction of actin polymerization and the formation of branched actin networks constitute the basis for membrane protrusion and cell motility (2,10,11).…”

p21Waf1is required for cellular senescence but not for cell cycle arrest induced by the HDAC inhibitor sodium butyrate

“…40,41 Ras-transformed cells demonstrate actin cytoskeleton disorganization and severing of F-actin. 42 We have earlier shown total severing of F-actin in rat E1A + cHa-Ras cells. 43 mERas-Waf1 +/+ cells respond to NaB treatment by accumulation of focal adhesions and appearance of F-actin, which drives changes in cell shape that are important for a variety of morphogenetic events, including cell migration.…”