Who Pix up Rac1?

Members of the large family of Rho GTPases are master regulators of the cytoskeletal changes necessary for cell adhesion, migration, and division. On page 759, ten Klooster et al. show how the activity of a Rho GTPase is spatially restricted by its COOH-terminal domain. The findings suggest that this highly variable region might provide the zip code for many different Rho members.

The COOH-terminal domain is known for its lipid-anchoring ability. But since membranes abound in the cell, that ability did not explain the specific localization of different GTPases. A COOH-terminal peptide of Rac1 had been shown to disrupt normal Rac1 activity, so the authors used this domain to pull down interacting proteins. The screen picked up Rac1's own activator, an exchange factor called β-Pix.

β-Pix was found in focal adhesions at the leading...