Abstract
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.
MeSH Terms
3T3 Cells
Adrenomedullin
Amino Acid Sequence
Animals
Biological Transport
Calcitonin/chemistry,metabolism
Calcitonin Gene-Related Peptide/genetics,metabolism
Calcitonin Receptor-Like Protein
Cell Line
Cloning, Molecular
Cross-Linking Reagents
Cystic Fibrosis Transmembrane Conductance Regulator/metabolism
Gene Expression
Glycosylation
Humans
Intracellular Signaling Peptides and Proteins
Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase/metabolism
Membrane Proteins/genetics,metabolism
Mice
Molecular Sequence Data
Peptides/metabolism
RNA, Messenger/metabolism
Receptor Activity-Modifying Protein 1
Receptor Activity-Modifying Protein 2
Receptor Activity-Modifying Proteins
Receptors, Adrenomedullin
Receptors, Calcitonin/metabolism
Receptors, Calcitonin Gene-Related Peptide/genetics,metabolism
Receptors, Peptide
Sequence Alignment
Tumor Cells, Cultured
Xenopus
Chemicals
CALCRL protein, human
CFTR protein, human
Calcitonin Receptor-Like Protein
Calcrl protein, mouse
Cross-Linking Reagents
Intracellular Signaling Peptides and Proteins
Membrane Proteins
Peptides
RAMP1 protein, human
RAMP2 protein, human
RNA, Messenger
Ramp1 protein, mouse
Ramp2 protein, mouse
Receptor Activity-Modifying Protein 1
Receptor Activity-Modifying Protein 2
Receptor Activity-Modifying Proteins
Receptors, Adrenomedullin
Receptors, Calcitonin
Receptors, Calcitonin Gene-Related Peptide
Receptors, Peptide
Cystic Fibrosis Transmembrane Conductance Regulator
Adrenomedullin
Calcitonin
Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase
Calcitonin Gene-Related Peptide
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
McLatchie L M
Receptor Systems and Cell Biology Units, Glaxo Wellcome Medicines Research Centre, Stevenage, Hertfordshire, UK.
Fraser N J
Main M J
Wise A
Brown J
Thompson N
Solari R
Lee M G
Foord S M