44
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor.

      Nature
      3T3 Cells, Adrenomedullin, Amino Acid Sequence, Animals, Biological Transport, Calcitonin, chemistry, metabolism, Calcitonin Gene-Related Peptide, genetics, Calcitonin Receptor-Like Protein, Cell Line, Cloning, Molecular, Cross-Linking Reagents, Cystic Fibrosis Transmembrane Conductance Regulator, Gene Expression, Glycosylation, Humans, Intracellular Signaling Peptides and Proteins, Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase, Membrane Proteins, Mice, Molecular Sequence Data, Peptides, RNA, Messenger, 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, Sequence Alignment, Tumor Cells, Cultured, Xenopus

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Most cited references21

          • Record: found
          • Abstract: found
          • Article: not found

          Signal-mediated sorting of membrane proteins between the endoplasmic reticulum and the golgi apparatus.

          Each organelle of the secretory pathway is required to selectively allow transit of newly synthesized secretory and plasma membrane proteins and also to maintain a unique set of resident proteins that define its structural and functional properties. In the case of the endoplasmic reticulum (ER), residency is achieved in two ways: (a) prevention of residents from entering newly forming transport vesicles and (b) retrieval of those residents that escape. The latter mechanism is directed by discrete retrieval motifs: Soluble proteins have a H/KDEL sequence at their carboxy-terminus; membrane proteins have a dibasic motif, either di-lysine or di-arginine, located close to the terminus of their cytoplasmic domain. Recently it was found that di-lysine motifs bind the complex of cytosolic coat proteins, COP I, and that this interaction functions in the retrieval of proteins from the Golgi to the ER. Also discussed are the potential roles this interaction may have in vesicular trafficking.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Expression cloning of an adenylate cyclase-coupled calcitonin receptor.

            A calcitonin receptor complementary DNA (cDNA) was cloned by expression of a cDNA library from a porcine kidney epithelial cell line in COS cells. The 482-amino acid receptor has high affinity for salmon calcitonin (dissociation constant Kd approximately 6 nM) and is functionally coupled to increases in intracellular cyclic adenosine monophosphate (cAMP). The receptor shows no sequence similarity to other reported G protein-coupled receptors but is homologous to the parathyroid hormone-parathyroid hormone-related peptide (PTH-PTHrP) receptor, indicating that the receptors for these hormones, which regulate calcium homeostasis, represent a new family of G protein-coupled receptors.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              A cDNA encoding the calcitonin gene-related peptide type 1 receptor.

              Calcitonin gene-related peptide (CGRP) is a neuropeptide with diverse biological effects including potent vasodilator activity. We report here the cloning of a complementary DNA (cDNA) encoding a human CGRP1 receptor, which shares significant peptide sequence homology with the human calcitonin receptor, a member of the G-protein-coupled receptor superfamily. Northern blot analysis revealed that the messenger RNA for this receptor is predominantly expressed in the lung and heart. In situ studies showed specific localization of the receptor mRNA to alveolar cells in the lung and to cardiac myocytes in the heart. Stable expression of the cDNA in human embryonic kidney 293 (HEK 293) cells produced specific, high affinity binding sites for CGRP that displayed pharmacological and functional properties very similar to native human CGRP1 receptor. Exposure of these cells to CGRP resulted in a 60-fold increase in cAMP production, which was inhibited in a competitive manner by the CGRP1 receptor antagonist, CGRP-(8-37).
                Bookmark

                Author and article information

                Comments

                Comment on this article