Receptors for calcitonin gene-related peptide, adrenomedullin, and amylin: the contributions of novel receptor-activity-modifying proteins.
The discovery of receptor-activity-modifying proteins (RAMP) revealed a new principle for the function of G protein-coupled receptors. The initially orphan calcitonin receptor-like receptor (CRLR) was identified as a CGRP receptor when coexpressed with RAMP1. The same receptor is specific for adrenomedullin (ADM) in the presence of RAMP2. Calcitonin receptors (CTR) with 60% homology to the CRLR predominantly recognize calcitonin in the absence of RAMP. An amylin/CGRP receptor was recognized when a calcitonin receptor (CTR) was coexpressed with RAMP1. In the presence of RAMP3, the CTR only interacts with amylin. Noncovalent association of the RAMP with the CRLR or the CTR reveals heterodimeric RAMP/receptor complexes at the cell surface. Thus, two Class II G protein-coupled receptors, the CRLR and CTR, associate with three RAMP to form high affinity receptors for CGRP, ADM, or amylin. Here, the molecular composition and the functional properties of these receptors is reviewed.
Born
W
W
Research Laboratory for Calcium Metabolism, Departments of Orthopedic Surgery and Medicine, University of Zurich, Klinik Balgrist, Forchstr. 340, 8008 Zurich, Switzerland. wborn@balgrist.unizh.ch
Fischer
J A
JA
Muff
R
R
D000818:Animals; D058286:Calcitonin Receptor-Like Protein; D003001:Cloning, Molecular; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D058262:Receptor Activity-Modifying Protein 1; D058263:Receptor Activity-Modifying Protein 2; D058264:Receptor Activity-Modifying Protein 3; D058261:Receptor Activity-Modifying Proteins; D058265:Receptors, Adrenomedullin; D018003:Receptors, Calcitonin / Q000235:genetics; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism*; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide / Q000378:metabolism*
C545578:CALCRL protein, human; D058286:Calcitonin Receptor-Like Protein; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; C545502:RAMP1 protein, human; C545503:RAMP2 protein, human; C545504:RAMP3 protein, human; D058262:Receptor Activity-Modifying Protein 1; D058263:Receptor Activity-Modifying Protein 2; D058264:Receptor Activity-Modifying Protein 3; D058261:Receptor Activity-Modifying Proteins; D058265:Receptors, Adrenomedullin; D018003:Receptors, Calcitonin; D018015:Receptors, Calcitonin Gene-Related Peptide; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide