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. In contrast, the molecular mechanisms underlying anterograde transport of newly synthesized GPCRs from the endoplasmic reticulum (ER) to the cell surface have just begun to be revealed. In this review, we will 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.

GGA3 Interacts with a G Protein-Coupled Receptor and Modulates Its Cell Surface Export

“…In agreement with this possibility, the same di-acidic motif has been demonstrated to interact with Sec24 and AP3 to control vesicular stomatitis virus protein G (VSVG) transport from the ER and the Golgi body, respectively (44,45). Nevertheless, this study, together with many other reports, indicates that GPCRs may directly interact with the transport machineries to control their export trafficking (23,24,46).…”

Rab26 Modulates the Cell Surface Transport of α2-Adrenergic Receptors from the Golgi

“…In addition, G protein-coupled olfactory and chemokine receptors are released from the ER but accumulated in the Golgi (14,15), and the opsin mutant E150K is accumulated in the cis and medial Golgi (16). Recent studies have also revealed that Ras-like small GTPases may play important roles in the Golgi to cell surface transport of GPCRs (17)(18)(19)(20)(21)(22).…”

New insights in the regulation of Rab GTPases by G protein-coupled receptors

“…2 During the last decade, many studies described the involvement of Rab GTPases in the regulation of GPCR trafficking and signaling. Rab GTPases were shown to be key regulators of GPCR anterograde and retrograde transport (Rab1, Rab2, Rab6, and Rab8), [3][4][5][6] endocytosis (Rab5), [7][8][9][10][11] recycling (Rab4 and Rab11), [11][12][13][14][15][16][17][18][19] and degradation (Rab7). 20 We and others established that a direct interaction between a GPCR and a Rab GTPase appears to be necessary in the proper trafficking of the receptor.…”