Identifying G Protein-Coupled Receptor Escorts, Chaperones, and Intracellular Tethers Regulating Receptor Density at the Cell Surface

G protein-coupled receptor (GPCR) responsiveness is dynamically regulated by various mechanisms, allowing fine-tuning of cell signaling. Modulation of GPCR plasma membrane density, via their release from intracellular compartments, constitutes a recently identified important process in this context. This phenomenon requires a complex network of interactions between GPCRs, “private” chaperones and escort proteins, and gatekeepers, which are directly involved in the retention of GPCRs in the intracellular compartments. The molecular and functional characterization of the players in this game is at its very beginning and requires appropriate quantitative methods of investigation to unravel the mechanisms that are involved.