Role of CGRP-Receptor Component Protein (RCP) in CLR/RAMP Function

The receptor for calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) requires an intracellular peripheral membrane protein named CGRP-receptor component protein (RCP) for signaling. RCP is required for CGRP and AM receptor signaling, and it has recently been discovered that RCP enables signaling by binding directly to the receptor. RCP is present in most immortalized cell lines, but in vivo RCP expression is limited to specific subsets of cells, usually co-localizing with CGRP-containing neurons. RCP protein expression correlates with CGRP efficacy in vivo, suggesting that RCP regulates CGRP signaling in vivo as it does in cell culture. RCP is usually identified in cytoplasm or membranes of cells, but recently has been observed in nucleus of neurons, suggesting an additional transcriptional role for RCP in cell function. Together, these data support an essential role for RCP in CGRP and AM receptor function, in which RCP expression enhances signaling of the CGRP or AM receptor, and therefore increases the efficacy of CGRP and AM in vivo.