WASP takes the sting out of SCAR mutants

WASP takes the sting out of SCAR mutants V eltman et al. reveal how one actin regulator can fi ll in for another to maintain cell protrusion and migration. The Arp2/3 complex stimulates actin assembly at several different sites within the cell. WASP family proteins activate the complex at clathrin-coated pits undergoing endocytosis, whereas SCAR/WAVE proteins stimulate Arp2/3's activity at the leading edge to promote membrane protrusion and cell migration. Yet SCAR-defi cient Dictyostelium cells still form protrusive pseudopods and migrate effi ciently toward a chemoattractant. Veltman et al. wondered whether WASP might assume the responsibility of regulating cell protrusion in Dictyostelium cells lacking SCAR. Sure enough, though WASP never localized to pseudopods in wild-type cells, the protein redeployed to the leading edge of SCAR knockouts, where it colocalized with the Arp2/3 complex. SCAR is usually recruited and activated by a quartet of regulatory proteins, but WASP didn't require any of these factors to localize to pseudopods. Instead, WASP was recruited to the leading edge by the Rac GTPase, a key regulator of cell migration that activates SCAR in wild-type protrusions. Rac was more active in SCAR knockouts, suggesting that SCAR usually induces a negative feedback loop to restrict Rac activity. In the absence of SCAR, Rac activity rises to the point that it can recruit WASP as a substitute activator of Arp2/3 and membrane protrusion. Actin regulatory pathways therefore aren't as separate as previously thought. Author Robert Insall now wants to investigate what other upstream signals regulate SCAR or, if necessary, WASP to successfully guide Dictyostelium chemotaxis. GW220 seals the fate of mRNAs C astilla-Llorente et al. identify a protein that determines the localization and fate of miRNA-targeted mRNAs. miRNAs silence their target mRNAs by incorporating them into silencing complexes (miRISCs) that contain members of the Argonaute and GW families of proteins. Once inside an miRISC, an mRNA can be translationally repressed or permanently degraded, but how these alternative fates are coordinated is unclear. Castilla-Llorente et al. shed light on this question when they identifi ed a unique GW protein splice variant called GW220. GW proteins have been associated with the formation of cyto-plasmic ribonucleoprotein granules called P bodies, but Castilla-Llorente et al. found that not all P bodies contain GW proteins. Instead, GW220 localized to a distinct class of P bodies that also contained Argonaute proteins and miRNA-targeted mRNAs. These " GW/P bodies " were much more stable …