A Gβγ Effector, ElmoE, Transduces GPCR Signaling to the Actin Network during Chemotaxis

Activation of G protein-coupled receptors (GPCRs) leads to the dissociation of heterotrimeric G-proteins into G alpha and G beta gamma subunits, which go on to regulate various effectors involved in a panoply of cellular responses. During chemotaxis, G beta gamma subunits regulate actin assembly and migration, but the protein(s) linking G beta gamma to the actin cytoskeleton remains unknown. Here, we identified a G beta gamma effector, ElmoE in Dictyostelium, and demonstrated that it is required for GPCR-mediated chemotaxis. Remarkably, ElmoE associates with G beta gamma and Dock-like proteins to activate the small GTPase Rac, in a GPCR-dependent manner, and also associates with Arp2/3 complex and F-actin. Thus, ElmoE serves as a link between chemoattractant GPCRs, G-proteins and the actin cytoskeleton. The pathway, consisting of GPCR, G beta gamma, Elmo/Dock, Rac, and Arp2/3, spatially guides the growth of dendritic actin networks in pseudopods of eukaryotic cells during chemotaxis.