Skip to main content

Ramp

  • Reference work entry
  • First Online:
  • 334 Accesses

Synonyms

Receptor (calcitonin) activity modifying protein; Receptor activity-modifying protein

Historical Background

The receptor activity-modifying protein (RAMP) family was first reported in 1998 during attempts to identify the cell surface receptor for a neuropeptide known as calcitonin gene-related peptide (CGRP) (McLatchie et al. 1998). Formerly, a protein known as the calcitonin receptor-like receptor (CLR) was thought to be the receptor for CGRP, but no study had convincingly shown that this was the case. McLatchie and colleagues were able to show that CLR needs RAMP1 for a CGRP receptor to be formed. RAMP1 assists CLR in reaching the cell surface. Thus, RAMP1 and CLR together at the cell surface form the receptor for CGRP, which binds and activates this protein complex, leading to downstream signaling events such as an accumulation of intracellular cAMP. In this same study, two other related proteins were found, named RAMP2 and RAMP3. Each of these proteins could also assist...

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   4,499.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   4,499.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Booe JM, Walker CS, Barwell J, Kuteyi G, Simms J, Jamaluddin MA, Warner ML, Bill RM, Harris PW, Brimble MA, Poyner DR, Hay DL, Pioszak AA. Structural basis for receptor activity-modifying protein-dependent selective peptide recognition by a G protein-coupled receptor. Mol Cell. 2015;58(6):1040–52. https://doi.org/10.1016/j.molcel.2015.04.018.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bomberger JM, Parameswaran N, Hall CS, Aiyar N, Spielman WS. Novel function for receptor activity-modifying proteins (RAMPs) in post-endocytic receptor trafficking. J Biol Chem. 2005;280:9297–307.

    Article  PubMed  CAS  Google Scholar 

  • 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;118:4709–20.

    Article  PubMed  CAS  Google Scholar 

  • Christopoulos A, Christopoulos G, Morfis M, Udawela M, Laburthe M, Couvineau A, Kuwasako K, Tilakaratne N, Sexton PM. Novel receptor partners and function of receptor activity-modifying proteins. J Biol Chem. 2003;278:3293–7.

    Article  CAS  PubMed  Google Scholar 

  • Dackor R, Fritz-Six K, Smithies O, Caron K. Receptor activity-modifying proteins 2 and 3 have distinct physiological functions from embryogenesis to old age. J Biol Chem. 2007;282:18094–9.

    Article  PubMed  CAS  Google Scholar 

  • Eftekhari S, Salvatore CA, Calamari A, Kane SA, Tajti J, Edvinsson L. Differential distribution of calcitonin gene-related peptide and calcitonin gene-related peptide receptor components (calcitonin receptor-like receptor and receptor activity-modifying protein 1) in the human trigeminal ganglion. Neuroscience. 2010;169:683–96.

    Article  CAS  PubMed  Google Scholar 

  • Fritz-Six KL, Dunworth WP, Li M, Caron KM. Adrenomedullin signaling is necessary for murine lymphatic vascular development. J Clin Invest. 2008;118:40–50.

    Article  PubMed  CAS  Google Scholar 

  • Hay DL, Pioszak AA. Receptor activity-modifying proteins (RAMPs): new insights and roles. Annu Rev Pharmacol Toxicol. 2016;56:469–87. https://doi.org/10.1146/annurev-pharmtox-010715-103120.

    Article  PubMed  CAS  Google Scholar 

  • Johnson EC, Shafer OT, Trigg JS, Park J, Schooley DA, Dow JA, Taghert PH. A novel diuretic hormone receptor in Drosophila: evidence for conservation of CGRP signaling. J Exp Biol. 2005;208:1239–46.

    Article  PubMed  CAS  Google Scholar 

  • Koth CM, Abdul-Manan N, Lepre CA, Connolly PJ, Yoo S, Mohanty AK, Lippke JA, Zwahlen J, Coll JT, Doran JD, Garcia-Guzman M, Moore JM. Refolding and characterization of a soluble ectodomain complex of the calcitonin gene-related peptide receptor. Biochemistry. 2010;49:1862–72.

    Article  PubMed  CAS  Google Scholar 

  • Kusano S, Kukimoto-Niino M, Akasaka R, Toyama M, Terada T, Shirouzu M, Shindo T, Yokoyama S. Crystal structure of the human receptor activity-modifying protein 1 extracellular domain. Protein Sci. 2008;17:1907–14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • McLatchie LM, Fraser NJ, Main MJ, Wise A, Brown J, Thompson N, Solari R, Lee MG, Foord SM. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature. 1998;393:333–9.

    Article  PubMed  CAS  Google Scholar 

  • Morfis M, Tilakaratne N, Furness SG, Christopoulos G, Werry TD, Christopoulos A, Sexton PM. Receptor activity modifying proteins differentially modulate the G protein-coupling efficiency of amylin receptors. Endocrinology. 2008;149:5423–31.

    Article  PubMed  CAS  Google Scholar 

  • Nag K, Kato A, Nakada T, Hoshijima K, Mistry AC, Takei Y, Hirose S. Molecular and functional characterization of adrenomedullin receptors in pufferfish. Am J Phys Regul Integr Comp Phys. 2006;290:R467–78.

    CAS  Google Scholar 

  • Poyner DR, Sexton PM, Marshall I, Smith DM, Quirion R, Born W, Muff R, Fischer JA, Foord SM, International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors. Pharmacol Rev. 2002;54:233–46.

    Article  PubMed  CAS  Google Scholar 

  • Sexton PM, Poyner DR, Simms J, Christopoulos A, Hay DL. Modulating receptor function through RAMPs: can they represent drug targets in themselves? Drug Discov Today. 2009;14:413–9.

    Article  PubMed  CAS  Google Scholar 

  • Tam CW, Husmann K, Clark NC, Clark JE, Lazar Z, Ittner LM, Götz J, Douglas G, Grant AD, Sugden D, Poston L, Poston R, McFadzean I, Marber MS, Fischer JA, Born W, Brain SD. Enhanced vascular responses to adrenomedullin in mice overexpressing receptor-activity-modifying protein 2. Circ Res. 2006;98:262–70.

    Article  PubMed  CAS  Google Scholar 

  • Walker CS, Eftekhari S, Bower RL, Wilderman A, Insel PA, Edvinsson L, Waldvogel HJ, Jamaluddin MA, Russo AF, Hay DL. A second trigeminal CGRP receptor: function and expression of the AMY1 receptor. Ann Clin Trans Neurol. 2015;2(6):595–608. doi:10.1002/acn3.197.

    Article  CAS  Google Scholar 

  • Zhang Z, Winborn CS, Marquez de Prado B, Russo AF. Sensitization of calcitonin gene-related peptide receptors by receptor activity-modifying protein-1 in the trigeminal ganglion. J Neurosci. 2007;27:2693–703.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Debbie L. Hay .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Hay, D.L., Sexton, P.M., Poyner, D.R. (2018). Ramp. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_112

Download citation

Publish with us

Policies and ethics