Regulation of G protein-coupled receptor trafficking and signaling by Rab GTPases

Abstract

Rab GTPases play an essential role in the regulation of intracellular transport including the budding, tethering, and fusion of vesicles as well as organelle motility. The regulation of G protein-coupled receptor (GPCR) trafficking by Rab GTPases has traditionally been regarded as a non-specific process that facilitates the movement of the receptors between intracellular membrane compartments. Thus, alterations in GPCR signal transduction and trafficking following the overexpression of constitutively active and dominant negative Rabs were originally considered to be solely the passive by-product of perturbations in intracellular compartmental dynamics. Recently, an explosion of experimental studies has provided increasingly convincing evidence that receptor trafficking actively affects the signal transduction of cargo proteins and that the signaling of GPCR vesicular cargo can in turn modulate Rab GTPase regulated intracellular transport processes. This research is revealing how different Rabs coordinate with themselves and other regulatory molecules to mediate protein trafficking, as well as uncovers novel functions for traditional Rabs, while illustrating the active role these trafficking molecules play in pathology of disease. Recently published in the Journal of Neuroscience, Esseltine et al., present a novel role for the typified exocytic small G protein Rab8 in the intracellular trafficking and signal transduction of metabotropic glutamate receptor 1.

Keywords: :

• G protein-coupled receptors
• Rab GTPase
• desensitization
• endocytosis
• glutamate
• signaling
• trafficking

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Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

This work was supported by operating grants to S.S.G.F. from the Canadian Institutes of Health Research (CIHR) MOP 119437 and MOP 111093. J.L.E. was the recipient of an Ontario Graduate Studentship. S.S.G.F. holds a Tier I Canada Research Chair in Molecular Neurobiology and is a Career Investigator of the Heart and Stroke Foundation of Ontario.