Palmitoylation Modification Regulates G-protein-coupled Receptors Effects

G-protein-coupled receptors(GPCRs) are transmembrane proteins,hence a number of their structural and functional features are modulated by both proteins and lipids.S-palmitoylation,as a classical lipid modification,regulates diverse aspects of GPCRs by affecting the interaction between GPCRs and signal proteins or lipid molecules.It is defined as the addition of saturated 16-carbon palmitate acid to specific cysteine residues through the formation of a liable thioester bond.The palmitoylation/depalmitoylation dynamics is regulated reversibly by both the palmitoyl acyl transferases(PATs) and palmitoyl protein thioesterases under various physiological status.Many GPCRs are palmitoylated on cysteine residues present in their cytoplasmic termini.The insertion of palmitate into the cytoplasmic leaflet of the plasma membrane can create the fouth and/or the fifth intracellular loop,thus profoundly affecting GPCRs structure,trafficking,sorting,signaling,desensitisation,internalization and oligomerisation.Furthermore,the interplay between palmitoylation and other posttranslational modifications,such as phosphorylation,ubiquitination and nitrosylation,can regulate the function of GPCRs coordinatively.It is expected that the identification of enzymes involved in GPCRs palmitoylation dynamics will be a key to delineate the role of palmitoylation in regulating GPCRs functions.