WASP (green) colocalizes with the Arp2/3 complex (red) at the leading edge of a SCAR knockout cell.

WASP (green) colocalizes with the Arp2/3 complex (red) at the leading edge of a SCAR knockout cell.

Veltman et al. reveal how one actin regulator can fill 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-deficient Dictyostelium cells still form protrusive pseudopods and migrate efficiently 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.

References

References
Veltman
D.M.
et al
.
2012
.
J. Cell Biol.
.