RAMPs pp 1-11 | Cite as

Introduction to Ramps

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 744)

Abstract

Receptor activity modifying proteins (RAMPs) are single transmembrane proteins discovered for their role in the regulation of translocation of certain G-protein coupled receptors (GPCRs) to the plasma membrane. Since its discovery in 1998, several pivotal advances have been made in understanding the function of this family of proteins. This chapter provides a basic introduction to RAMPs as well as details on the various chapters in this book.

Keywords

Migraine Cysteine Serine Polypeptide Angiotensin 

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References

  1. 1.
    McLatchie LM, Fraser NJ, Main MJ et al. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 1998; 393(6683):333–339.PubMedCrossRefGoogle Scholar
  2. 2.
    Fluhmann B, Muff R, Hunziker W et al. A human orphan calcitonin receptor-like structure. Biochem Biophys Res Commun 1995; 206(1):341–347.PubMedCrossRefGoogle Scholar
  3. 3.
    Aiyar N, Rand K, Elshourbagy NA et al. A cDNA encoding the calcitonin gene-related peptide type 1 receptor. J Biol Chem 1996; 271(19):11325–11329.PubMedCrossRefGoogle Scholar
  4. 4.
    Parameswaran N, Spielman WS. RAMPs: The past, present and future. Trends Biochem Sci 2006; 31(11):631–638.PubMedCrossRefGoogle Scholar
  5. 5.
    Christopoulos A, Christopoulos G, Morfis M et al. Novel receptor partners and function of receptor activity-modifying proteins. J Biol Chem 2003; 278(5):3293–3297.PubMedCrossRefGoogle Scholar
  6. 6.
    Harikumar KG, Simms J, Christopoulos G et al. Molecular basis of association of receptor activity-modifying protein 3 with the family B G protein-coupled secretin receptor. Biochemistry 2009; 48(49):11773–11785.PubMedCrossRefGoogle Scholar
  7. 7.
    Bouschet T, Martin S, Henley JM. Receptor-activity-modifying proteins are required for forward trafficking of the calcium-sensing receptor to the plasma membrane. J Cell Sci 2005; 118(Pt 20):4709–4720.PubMedCrossRefGoogle Scholar
  8. 8.
    ter Haar E, Koth CM, Abdul-Manan N et al. Crystal structure of the ectodomain complex of the CGRP receptor, a class-B GPCR, reveals the site of drug antagonism. Structure 2010; 18(9):1083–1093.PubMedCrossRefGoogle Scholar
  9. 9.
    Moore EL, Gingell JJ, Kane SA et al. Mapping the CGRP receptor ligand binding domain: tryptophan-84 of RAMP1 is critical for agonist and antagonist binding. Biochem Biophys Res Commun 2010; 394(1):141–145.PubMedCrossRefGoogle Scholar
  10. 10.
    Koth CM, Abdul-Manan N, Lepre CA et al. Refolding and characterization of a soluble ectodomain complex of the calcitonin gene-related peptide receptor. Biochemistry 2010; 49(9):1862–1872.PubMedCrossRefGoogle Scholar
  11. 11.
    Qi T, Simms J, Bailey RJ et al. Structure-function analysis of RAMP1-RAMP3 chimeras. Biochemistry 2010; 49(3):522–531.PubMedCrossRefGoogle Scholar
  12. 12.
    Barwell J, Miller PS, Donnelly D et al. Mapping interaction sites within the N-terminus of the calcitonin gene-related peptide receptor; the role of residues 23–60 of the calcitonin receptor-like receptor. Peptides 2010; 31(1):170–176.PubMedCrossRefGoogle Scholar
  13. 13.
    Chang CL, Park JI, Hsu SY. Activation of calcitonin receptor and calcitonin receptor-like receptor by membrane-anchored ligands. J Biol Chem 2010; 285(2):1075–1080.PubMedCrossRefGoogle Scholar
  14. 14.
    Simms J, Hay DL, Bailey RJ et al. Structure-function analysis of RAMP1 by alanine mutagenesis. Biochemistry 2009; 48(1):198–205.PubMedCrossRefGoogle Scholar
  15. 15.
    Conner AC, Simms J, Barwell J et al. Ligand binding and activation of the CGRP receptor. Biochem Soc Trans 2007; 35(Pt 4):729–732.PubMedGoogle Scholar
  16. 16.
    Conner AC, Simms J, Conner MT et al. Diverse functional motifs within the three intracellular loops of the CGRP1 receptor. Biochemistry 2006; 45(43):12976–12985.PubMedCrossRefGoogle Scholar
  17. 17.
    Banerjee S, Evanson J, Harris E et al. Identification of specific calcitonin-like receptor residues important for calcitonin gene-related peptide high affinity binding. BMC Pharmacol 2006; 6:9.PubMedCrossRefGoogle Scholar
  18. 18.
    Simms J, Hay DL, Wheatley M et al. Characterization of the structure of RAMP1 by mutagenesis and molecular modeling. Biophys J 2006; 91(2):662–669.PubMedCrossRefGoogle Scholar
  19. 19.
    Ittner LM, Koller D, Muff R et al. The N-terminal extracellular domain 23–60 of the calcitonin receptor-like receptor in chimeras with the parathyroid hormone receptor mediates association with receptor activity-modifying protein 1. Biochemistry 2005; 44(15):5749–5754.PubMedCrossRefGoogle Scholar
  20. 20.
    Ittner LM, Luessi F, Koller D et al. Aspartate(69) of the calcitonin-like receptor is required for its functional expression together with receptor-activity-modifying proteins 1 and-2. Biochem Biophys Res Commun 2004; 319(4):1203–1209.PubMedCrossRefGoogle Scholar
  21. 21.
    Steiner S, Born W, Fischer JA et al. The function of conserved cysteine residues in the extracellular domain of human receptor-activity-modifying protein. FEBS Lett 2003; 555(2):285–290.PubMedCrossRefGoogle Scholar
  22. 22.
    Koller D, Born W, Leuthauser K et al. The extreme N-terminus of the calcitonin-like receptor contributes to the selective interaction with adrenomedullin or calcitonin gene-related peptide. FEBS Lett 2002; 531(3):464–468.PubMedCrossRefGoogle Scholar
  23. 23.
    Miller PS, Barwell J, Poyner DR et al. Non-peptidic antagonists of the CGRP receptor, BIBN4096BS and MK-0974, interact with the calcitonin receptor-like receptor via methionine-42 and RAMP1 via tryptophan-74. Biochem Biophys Res Commun 2010; 391(1):437–442.PubMedCrossRefGoogle Scholar
  24. 24.
    Salvatore CA, Mallee JJ, Bell IM et al. Identification and pharmacological characterization of domains involved in binding of CGRP receptor antagonists to the calcitonin-like receptor. Biochemistry 2006; 45(6):1881–1887.PubMedCrossRefGoogle Scholar
  25. 25.
    Rajagopal S, Rajagopal K, Lefkowitz RJ. Teaching old receptors new tricks: biasing seven-transmembrane receptors. Nat Rev Drug Discov 2010; 9(5):373–386.PubMedCrossRefGoogle Scholar
  26. 26.
    Reiter E, Lefkowitz RJ. GRKs and beta-arrestins: roles in receptor silencing, trafficking and signaling. Trends Endocrinol Metab 2006; 17(4):159–165.PubMedCrossRefGoogle Scholar
  27. 27.
    Lefkowitz RJ, Rajagopal K, Whalen EJ. New roles for beta-arrestins in cell signaling: not just for seven-transmembrane receptors. Mol Cell 2006; 24(5):643–652.PubMedCrossRefGoogle Scholar
  28. 28.
    Cottrell GS, Padilla B, Pikios S et al. Post-endocytic sorting of calcitonin receptor-like receptor and receptor activity-modifying protein 1. J Biol Chem 2007; 282(16):12260–12271.PubMedCrossRefGoogle Scholar
  29. 29.
    Kuwasako K, Cao YN, Chu CP et al. Functions of the cytoplasmic tails of the human receptor activity-modifying protein components of CGRP and adrenomedullin receptors. J Biol Chem 2006.Google Scholar
  30. 30.
    Bomberger JM, Spielman WS, Hall CS et al. Receptor activity-modifying protein (RAMP) isoform-specific regulation of adrenomedullin receptor trafficking by NHERF-1. J Biol Chem 2005; 280(25):23926–23935.PubMedCrossRefGoogle Scholar
  31. 31.
    Bomberger JM, Parameswaran N, Hall CS et al. Novel function for receptor activity-modifying proteins (RAMPs) in post-endocytic receptor trafficking. J Biol Chem 2005; 280(10):9297–9307.PubMedCrossRefGoogle Scholar
  32. 32.
    Hilairet S, Belanger C, Bertrand J et al. Agonist-promoted internalization of a ternary complex between calcitonin receptor-like receptor, receptor activity-modifying protein 1 (RAMP1) and beta-arrestin. J Biol Chem 2001; 276(45):42182–42190.PubMedCrossRefGoogle Scholar
  33. 33.
    Kuwasako K, Kitamura K, Nagata S et al. Flow cytometric analysis of the calcitonin receptor-like receptor domains responsible for cell-surface translocation of receptor activity-modifying proteins. Biochem Biophys Res Commun 2009; 384(2):249–254.PubMedCrossRefGoogle Scholar
  34. 34.
    Tsujikawa K, Yayama K, Hayashi T et al. Hypertension and dysregulated proinflammatory cytokine production in receptor activity-modifying protein 1-deficient mice. Proc Natl Acad Sci U S A 2007; 104(42):16702–16707.PubMedCrossRefGoogle Scholar
  35. 35.
    Ichikawa-Shindo Y, Sakurai T, Kamiyoshi A et al. The GPCR modulator protein RAMP2 is essential for angiogenesis and vascular integrity. J Clin Invest 2008; 118(1):29–39.PubMedCrossRefGoogle Scholar
  36. 36.
    Fritz-Six KL, Dunworth WP, Li M et al. Adrenomedullin signaling is necessary for murine lymphatic vascular development. J Clin Invest 2008; 118(1):40–50.PubMedCrossRefGoogle Scholar
  37. 37.
    Dackor R, Fritz-Six K, Smithies O et al. Receptor activity-modifying proteins 2 and 3 have distinct physiological functions from embryogenesis to old age. J Biol Chem 2007; 282(25):18094–18099.PubMedCrossRefGoogle Scholar
  38. 38.
    Zhang Z, Winborn CS, Marquez de Prado B et al. Sensitization of calcitonin gene-related peptide receptors by receptor activity-modifying protein-1 in the trigeminal ganglion. J Neurosci 2007; 27(10):2693–2703.PubMedCrossRefGoogle Scholar
  39. 39.
    Tam CW, Husmann K, Clark NC et al. Enhanced vascular responses to adrenomedullin in mice overexpressing receptor-activity-modifying protein 2. Circ Res 2005.Google Scholar
  40. 40.
    Saito H, Kubota M, Roberts RW et al. RTP family members induce functional expression of mammalian odorant receptors. Cell 2004; 119(5):679–691.PubMedCrossRefGoogle Scholar
  41. 41.
    Bonner K, Kariyawasam HH, Ali FR et al. Expression of functional receptor activity modifying protein 1 by airway epithelial cells with dysregulation in asthma. J Allergy Clin Immunol 2010; 126(6):1277–1283, e1273.PubMedCrossRefGoogle Scholar
  42. 42.
    Brekhman V, Lugassie J, Zaffryar-Eilot S et al. Receptor activity modifying protein-3 mediates the protumorigenic activity of lysyl oxidase-like protein-2. FASEB J 2011; 25(1):55–65.PubMedCrossRefGoogle Scholar
  43. 43.
    Chrissobolis S, Zhang Z, Kinzenbaw DA et al. Receptor activity-modifying protein-1 augments cerebrovascular responses to calcitonin gene-related peptide and inhibits angiotensin II-induced vascular dysfunction. Stroke 2010; 41(10):2329–2334.PubMedCrossRefGoogle Scholar
  44. 44.
    Sabharwal R, Zhang Z, Lu Y et al. Receptor activity-modifying protein 1 increases baroreflex sensitivity and attenuates Angiotensin-induced hypertension. Hypertension 2010; 55(3):627–635.PubMedCrossRefGoogle Scholar
  45. 45.
    Husmann K, Sexton PM, Fischer JA et al. Mouse receptor-activity-modifying proteins 1,-2 and-3: amino acid sequence, expression and function. Mol Cell Endocrinol 2000; 162(1-2):35–43.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2012

Authors and Affiliations

  1. 1.Department of PhysiologyMichigan State UniversityEast LansingUSA

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