Excess coronin (red) drives actin (green) to form extended circular filaments.

The Arp2/3 protein complex is a central regulator of actin assembly. Although a number of Arp2/3 activators have been identified in recent years, Humphries et al., on page 993, are the first to find a direct inhibitor of the complex: the highly conserved actin cytoskeleton component coronin. Using a combination of biochemical and genetic strategies, the authors found that the yeast coronin protein Crn1 physically and functionally interacts with the Arp2/3 complex in vivo via an evolutionarily conserved coiled-coil domain of Crn1. Although Crn1 strongly inhibits Arp2/3-mediated nucleation of actin in vitro, the addition of preformed actin filaments overrides this inhibition.

Based on the results, Humphries et al. propose that Crn1 may spatially restrict the activity of Arp2/3, permitting nucleation of new filaments only from the sides of existing filaments. This would promote the growth of a branched actin filament network like those often seen at the leading edges of motile cells. The mechanism by which coronin exerts this effect is not clear, although biochemical experiments have ruled out a simple steric block of Arp2/3 binding to either activators or actin. ▪