Sorting Nexins: New Determinants for the Development of Hypertension - Abstract
G protein-coupled receptors (GPCRs) are serpentine seven-transmembrane receptors that mediate the cellular responses to a myriad of hormones and neurotransmitters. As such, many of these receptors are crucial to the regulation of important physiological processes, such as blood pressure and renal sodium transport. The trafficking and signal transduction of GPCRs, including the dopamine receptors, are tightly regulated to ensure the accuracy of the intracellular signal and to limit the specificity and extent of the cellular response. A growing body of evidence has shown that the sorting and intracellular trafficking of agonist-activated receptors, including the GPCRs, appear to be mediated by the sorting nexins, among a few other proteins. The sorting nexin family consists of a diverse group of cytoplasmic and membrane-associated proteins that contain the canonical phox homology (PX) domain and are involved in the various aspects of protein trafficking after receptor endocytosis. Perturbation of the process and/or deficiency of the proteins involved in GPCR trafficking and signaling may lead to receptor dysfunction, impaired homeostatic responses, and possibly disease state. In this review, we provide an overview of GPCR trafficking, highlight the sorting nexins that impact the GPCRs that are involved in blood pressure control, and expound on the mechanisms of how the loss of certain sorting nexins may eventually lead to hypertension.