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
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3T3 Cells
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Adrenomedullin
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Amino Acid Sequence
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Animals
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Biological Transport
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Calcitonin / chemistry
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Calcitonin / metabolism
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Calcitonin Gene-Related Peptide / genetics
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Calcitonin Gene-Related Peptide / metabolism*
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Calcitonin Receptor-Like Protein
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Cell Line
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Cloning, Molecular
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Cross-Linking Reagents
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Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
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Gene Expression
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Glycosylation
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Humans
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Intracellular Signaling Peptides and Proteins
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Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase / metabolism
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Molecular Sequence Data
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Peptides / metabolism*
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RNA, Messenger / metabolism
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Receptor Activity-Modifying Protein 1
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Receptor Activity-Modifying Protein 2
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Receptor Activity-Modifying Proteins
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Receptors, Adrenomedullin
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Receptors, Calcitonin / metabolism*
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Receptors, Calcitonin Gene-Related Peptide / genetics
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Receptors, Calcitonin Gene-Related Peptide / metabolism*
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Receptors, Peptide*
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Sequence Alignment
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Tumor Cells, Cultured
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Xenopus
Substances
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CALCRL protein, human
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CFTR protein, human
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Calcitonin Receptor-Like Protein
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Calcrl protein, mouse
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Cross-Linking Reagents
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Peptides
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RAMP1 protein, human
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RAMP2 protein, human
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RNA, Messenger
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Ramp1 protein, mouse
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Ramp2 protein, mouse
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Receptor Activity-Modifying Protein 1
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Receptor Activity-Modifying Protein 2
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Receptor Activity-Modifying Proteins
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Receptors, Adrenomedullin
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Receptors, Calcitonin
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Receptors, Calcitonin Gene-Related Peptide
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Receptors, Peptide
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Cystic Fibrosis Transmembrane Conductance Regulator
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Adrenomedullin
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Calcitonin
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Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase
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Calcitonin Gene-Related Peptide
Associated data
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GENBANK/AJ001014
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GENBANK/AJ001015
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GENBANK/AJ001016