Small GTPase regulation of GPCR anterograde trafficking

Abstract

The physiological functions of heterotrimeric G protein-coupled receptors (GPCRs) are dictated by their intracellular trafficking and precise targeting to the functional destinations. Over the past decades, most studies on the trafficking of GPCRs have focused on the events involved in endocytosis and recycling. By contrast, the molecular mechanisms underlying anterograde transport of newly synthesized GPCRs from the endoplasmic reticulum (ER) to the cell surface have only now begun to be revealed. In this review we discuss current advances in understanding the role of Ras-like GTPases, specifically the Rab and Sar1/ARF subfamilies, in regulating cell-surface transport of GPCRs en route from the ER and the Golgi.

Figure 1

Roles of small GTPases in the anterograde transport and signaling of GPCRs. (a) Rab1, Rab2, Rab6, Sar1, and ARF6 modulate the ER-to-Golgi traffic of GPCRs, whereas Rab8 and ARF4 regulate the Golgi-to-plasma membrane (PM) transport of GPCRs. ARF1 is involved in GPCR transport from the ER through the Golgi to the cell surface at multiple steps. Small GTPase-coordinated transport processes will dictate the cell-surface numbers of the receptors available for binding to hormones or drugs (●) and thus, will influence the magnitude of signal transduction and physiological/pharmacological responses mediated by the receptors. N, N terminus; C, C terminus. (b) Three possible pathways that mediate GPCR transport from the ER to the Golgi.