Receptors for chemokines and a variety of ligands such as histamine, nucleosides, and bioactive lipids signal through heterotrimeric G proteins and play critical roles in immune function. Heterotrimeric G protein signaling pathways are subjected to many layers of regulation including regulators of G protein signaling (RGS) proteins that mainly function to attenuate these signaling pathways. This review focuses on the overall importance of G protein-coupled receptor-heterotrimeric G protein-RGS protein signaling in immune function with emphasis on lymphocyte trafficking and motility. Considerable portion is devoted to discussing mechanisms by which chemoattractant receptors activate downstream signaling pathways that function during leukocyte migration. Studies using intravital imaging techniques to monitor lymphocyte trafficking and motility as well as ones probing intracellular spatiotemporal dynamics of trimeric signaling components are also discussed as they increasingly provide mechanistic insights into trimeric G protein signaling networks.
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