GRK Roles in C. elegans

G-protein-coupled receptor kinases (GRKs) are serine/threonine kinases that specifically phosphorylate activated (agonist bound) GPCRs to terminate signaling. Proteins of the arrestin family then bind to the phosphorylated receptor, blocking both receptor and G-protein reactivation. Thus, GRKs are critical regulators of GPCR signaling that function to protect cells against receptor overstimulation, maintain sensitivity to changing environmental signals and allow signal integration. When considering the extent to which C. elegans rely upon GPCR-mediated chemosensation to navigate their native environments, the involvement of GRKs in the regulation of C. elegans chemosensation is logical. While C. elegans grk-1 plays a minor modulatory role in dopamine signaling, C. elegans grk-2 is involved in numerous aspects of chemosensation, from regulation of specialized sensory structures to circadian control over chemosensory sensitivity. In this chapter, we discuss the functions of both in detail and, to avoid confusion with the mammalian gene names, we refer to the C. elegans genes as Ce-grk-1 and Ce-grk-2, respectively.