Cofilin Takes the Lead

Cofilin has emerged as a key regulator of actin dynamics at the leading edge of motile cells. Through its actin-severing 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 14-3-3zeta 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.