Rho GTPase Activating Protein 18 (ARHGAP18)

ARHGAP18 belongs to a family of Rho GTPase-activating proteins that modulate cell signaling. By genomic sequence analysis, Potkin et al. (2009) mapped the ARHGAP18 gene to chromosome 6q22-q24.Myosin was involved in Rac control of directionality but not in Rac-induced protrusion, whereas PAK was required for Rac-induced protrusion. PA-Rac1 was used to elucidate Rac regulation of RhoA in cell motility. Rac and Rho coordinate cytoskeletal behaviors with seconds and submicrometer precision. Rac was shown to inhibit RhoA in mouse embryonic fibroblasts, with inhibition modulated at protrusions and ruffles. A PA-Rac crystal structure and modeling revealed LOV-Rac interactions that will facilitate extension of this photoactivation approach to other proteins.