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Trafficking of G-protein-coupled receptors to the plasma membrane: insights for pharmacoperone drugs Conn PM; Ulloa-Aguirre ATrends Endocrinol Metab 2010[Mar]; 21 (3): 190-7G protein-coupled receptors (GPCRs) are among the most common potential targets for pharmacological design. Synthesized in the endoplasmic reticulum, they interact with endogenous chaperones that assist in folding (or can retain incorrectly folded proteins) and are transferred to the plasma membrane where they exert their physiological functions. We summarize trafficking of the gonadotropin-releasing hormone receptor (GnRHR) to the plasma membrane. The trafficking of GnRHR is among the best characterized due in part to its small size and the consequent ease of making mutant proteins. Human mutations that cause disease through the misrouting of GPCRs including GnRHR are also reviewed. Special emphasis is placed on therapeutic opportunities presented by pharmacological chaperone drugs, or pharmacoperones, that allow misrouted mutants to be routed correctly and restored to function.|Animals[MESH]|Cell Membrane/*metabolism[MESH]|Humans[MESH]|Models, Biological[MESH]|Protein Folding[MESH]|Protein Transport/*physiology[MESH]|Receptors, G-Protein-Coupled/chemistry/genetics/*metabolism[MESH]|Receptors, LHRH/chemistry/genetics/metabolism[MESH] |
