Abstract
The renal dopaminergic system has been identified as a modulator of sodium balance and blood pressure. According to the Centers for Disease Control and Prevention, in 2018 in the United States, almost half a million deaths included hypertension as a primary or contributing cause. Renal dopamine receptors, members of the G protein-coupled receptor family, are divided in two groups: D1-like receptors that act to keep the blood pressure in the normal range, and D2-like receptors with a variable effect on blood pressure, depending on volume status. The renal dopamine receptor function is regulated, in part, by its expression in microdomains in the plasma membrane. Lipid rafts form platforms within the plasma membrane for the organization and dynamic contact of molecules involved in numerous cellular processes such as ligand binding, membrane sorting, effector specificity, and signal transduction. Understanding all the components of lipid rafts, their interaction with renal dopamine receptors, and their signaling process offers an opportunity to unravel potential treatment targets that could halt the progression of hypertension, chronic kidney disease (CKD), and their complications.
Highlights
The classical definition of a cell membrane is a semipermeable membrane, composed of a lipid bilayer mixed with proteins, that surrounds the cytoplasm and nucleoplasm
Lipid rafts and microcompartments in lipid rafts are important in the function of G protein-coupled receptors (GPCRs), including dopamine receptors
The dopamine receptor family is divided in two groups, all of which are expressed in the kidney, D1-like receptors (D1R and D5R) and D2-like receptors (D2R, D3R, and D4R)
Summary
The classical definition of a cell membrane is a semipermeable membrane, composed of a lipid bilayer mixed with proteins, that surrounds the cytoplasm and nucleoplasm. Lipid rafts (Figure 1) are dynamic and shifting assemblies of sphingolipids, cholesterol, glycosphingolipids, and proteins forming platforms or lipid microdomains for the organization and dynamic contact of molecules involved in several molecular and cellular processes such as ligand affinity, effector specificity, signal transduction, membrane sorting, and receptor trafficking and recycling. Caveolae (Figure 2) are scaffolding proteins that assemble within lipid raft domains to form flask-shaped invaginations of the plasma membrane These platforms allow protein–protein, lipid–lipid, and protein–lipid interactions and regulate numerous cellular processes (signal transduction, receptor trafficking, recycling, etc.). The CRAC motif helps anchor the Cav isoforms to the plasma membrane [12] as well as other plasma proteins, including GPCRs. Once the GPCR is targeted to a lipid raft, it can be successfully stimulated by interacting with its ligand (Figure 3). The SNX either sorts the endocytosed and dephosphorylated/resensitized GPCR into the fast recycling endosomes, targeting it to lipid rafts (Figure 9), or send such receptor to late endosomes, targeting it to lysosomes, inducing the inevitable degradation of the GPCR [17]
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