Regulation of calcium-sensing-receptor trafficking and cell-surface expression by GPCRs and RAMPs

The calcium-sensing (CaS) receptor is a G-protein-coupled receptor (GPCR) that is of fundamental importance for extracellular calcium signalling and calcium homeostasis. The CaS receptor detects changes in free, ionized extracellular calcium concentration and initiates pathways that constantly re-adjust levels of circulating calcium. In addition, the CaS receptor is involved in processes such as stem-cell homing and regulation of neuronal-process outgrowth. To perform these functions, the CaS receptor must be appropriately targeted to the plasma membrane so that its large N-terminal calcium-sensing domain is positioned in the extracellular environment to detect dynamic changes in ionic calcium concentration. Here, we provide an overview of the molecular determinants controlling CaS receptor forward traffic and highlight the roles of CaS receptor interactors such as receptor-activity-modifying proteins and subunits of other class C GPCRs in this process.