Cell-to-cell variations in subcellular localisation of V2R are independent of its expression level

Abstract

G protein coupled receptors (GPCRs) translate the actions of hormones and neurotransmitters into intracellular signalling events. Mutations in GPCRs can prevent their correct expression and trafficking to the cell surface and cause disease. Single cell subcellular localisation measurements reveal that while some cells appear to traffic the majority of the vasopressin 2 receptor (V2R) molecules to the cell surface, others retain a greater number of receptors in the ER or have approximately equal distribution. Mutations in the V2R affect the proportion of cells able to send this GPCR to their cell surface but surprisingly they do not prevent all cells from correctly trafficking the mutant receptors. These findings reveal the potential for rescue of mutant receptor cell surface expression by pharmacological manipulation of the GPCR folding and trafficking machinery.