Regulation of GPCR signal networks via membrane trafficking.
G-protein-coupled receptors (GPCRs) are a superfamily of cell surface signaling proteins that act as central molecular activators and integrators in all endocrine systems. Membrane trafficking of GPCRs is a fundamental process in shaping extensive signaling networks activated by these receptors. Mounting evidence has identified an increasingly complex network of pathways and protein interactions that a GPCR can traverse and associate with, indicating a multi-level system of regulation. This review will discuss the recent developments in how GPCRs are trafficked to the cell surface as newly synthesized receptors, their recruitment to the clathrin-mediated pathway for endocytosis, and their sorting to subsequent divergent post-endocytic fates, focusing primarily on hormone-activated GPCRs. Current models depicting the classic roles membrane trafficking plays in GPCR signaling have evolved to a highly regulated and complex system than previously appreciated. These developments impart key mechanistic information on how spatial and temporal aspects of GPCR signaling may be integrated and could provide pathway-specific targets to be exploited for therapeutic intervention.
Jean-Alphonse
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Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
Hanyaloglu
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D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D021381:Protein Transport; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction
D008565:Membrane Proteins; D043562:Receptors, G-Protein-Coupled