RAMPS REGULATE THE TRANSPORT AND LIGAND SPECIFICITY OF THE CALCITONIN-RECEPTOR-LIKE RECEPTOR

Calcitonin-gene-related peptide (CORP) and adrenomedullin are related peptides with distinct pharmacological profiles. Here we show that a r eceptor with seven transmembrane domains, the calcitonin-receptor-like receptor (CRLR), can function as either a CORP receptor or an adrenom edullin 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 tra nsport CRLR to the plasma membrane. RAMP1 presents the receptor at the cell surface as a mature glycoprotein and a CORP receptor. RAMP2-tran sported receptors are core-glycosylated and are adrenomedullin recepto rs.