RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor

Calcitonin-gene-related peptide (CGRP) and Adrenomedullin are related peptides with distinct pharmacological profiles. Here we show that a receptor with seven transmembrane domains, the calcitonin-receptor-like receptor (CRLR), can function as either a CGRP Receptor or an Adrenomedullin receptor, depending on which members of a new family of single-transmembrane-domain proteins, which we have called receptor-activity-modifying proteins or RAMPs, are expressed. RAMPs are required to transport CRLR to the plasma membrane. RAMP1 presents the receptor at the cell surface as a mature glycoprotein and a CGRP Receptor. RAMP2-transported receptors are core-glycosylated and are Adrenomedullin receptors.