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.
McLatchie
L M
LM
Receptor Systems and Cell Biology Units, Glaxo Wellcome Medicines Research Centre, Stevenage, Hertfordshire, UK.
Fraser
N J
NJ
Main
M J
MJ
Wise
A
A
Brown
J
J
Thompson
N
N
Solari
R
R
Lee
M G
MG
Foord
S M
SM
D016475:3T3 Cells; D053607:Adrenomedullin; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002116:Calcitonin / Q000737:chemistry / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D058286:Calcitonin Receptor-Like Protein; D002460:Cell Line; D003001:Cloning, Molecular; D003432:Cross-Linking Reagents; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D015870:Gene Expression; D006031:Glycosylation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D058262:Receptor Activity-Modifying Protein 1; D058263:Receptor Activity-Modifying Protein 2; D058261:Receptor Activity-Modifying Proteins; D058265:Receptors, Adrenomedullin; D018003:Receptors, Calcitonin / Q000378:metabolism*; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D018000:Receptors, Peptide; D016415:Sequence Alignment; D014407:Tumor Cells, Cultured; D014981:Xenopus
C545578:CALCRL protein, human; C505032:CFTR protein, human; D058286:Calcitonin Receptor-Like Protein; C545579:Calcrl protein, mouse; D003432:Cross-Linking Reagents; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010455:Peptides; C545502:RAMP1 protein, human; C545503:RAMP2 protein, human; D012333:RNA, Messenger; C545505:Ramp1 protein, mouse; C545506:Ramp2 protein, mouse; D058262:Receptor Activity-Modifying Protein 1; D058263:Receptor Activity-Modifying Protein 2; D058261:Receptor Activity-Modifying Proteins; D058265:Receptors, Adrenomedullin; D018003:Receptors, Calcitonin; D018015:Receptors, Calcitonin Gene-Related Peptide; D018000:Receptors, Peptide; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D053607:Adrenomedullin; D002116:Calcitonin; D017038:Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase; D015740:Calcitonin Gene-Related Peptide