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

Nature volume 393, pages333–339(1998)Cite this article

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.

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Figure 1
Figure 2: Xenopus oocytes expressing RAMP1 show large and dose-dependent responses to CGRP.
Figure 3: Expression of RAMP1 with CRLR in oocytes and HEK293T cells.
Figure 4: RAMP1 and CRLR are localized together on the cell surface when they are co-expressed.
Figure 5: RAMP1 acts to increase the relative molecular mass of CRLR at the same time as specific binding to 125I-labelled CGRP1 becomes apparent.
Figure 6: Amino-acid sequences of human RAMPs 1, 2 and 3, aligned for comparison.
Figure 7: A northern blot analysis of mRNA encoding RAMPs 1, 2 and 3 in cell lines and tissues.
Figure 8: Expression of RAMP2 plus CRLR in oocytes and in HEK293T cells.
Figure 9

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Acknowledgements

We thank D. Cousens for probing the MTN blots; E. Murrison for help with cloningRAMP2; S. Brown for isolation of the CRLR/RAMP1 cell lines; J. M. Rommens and L. C. Tsui for CFTR; W. Born and J. Fischer for CRLR and for discussions; and members of the RSU for their support.

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  1. Linda M. McLatchie

    Present address: The Novartis Institute for Medical Sciences, 5 Gower Place, London, WC1E 6BN, UK

Affiliations

  1. Receptor Systems and Cell Biology Units, GlaxoWellcome Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, Hertfordshire, UK

    Linda M. McLatchie, Neil J. Fraser, Martin J. Main, Alan Wise, Jason Brown, Nicola Thompson, Roberto Solari, Melanie G. Lee & Steven M. Foord

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  1. Linda M. McLatchie
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Correspondence to Steven M. Foord.

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McLatchie, L., Fraser, N., Main, M. et al. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 393, 333–339 (1998). https://doi.org/10.1038/30666

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