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The Calcitonin Peptide Family: What Can We Learn from Receptor Knock Out and Transgenic Mice

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The calcitonin gene-related peptide family

Abstract

This review focuses on the biological relevance of receptors of the calcitonin (CT) family of peptides and respective ligands assessed in vivo through removal or overexpression of receptor components in mice. Receptors of the CT peptide family consist of the structurally related seven transmembrane-domain G protein-coupled CT- (CTR) or CT receptor-like (CLR) receptors and associated distinct receptor-activity-modifying proteins (RAMP)-1, -2 and -3 that modulate the ligand selectivity. The CTR alone binds CT and CT receptor-stimulating peptide-1 with high affinity. Besides, CTR/RAMP1 heterodimers are CT gene-related peptide (CGRP)/amylin receptors and CTR/RAMP3 heterodimers recognize amylin alone. CLR/RAMP1 and CLR/RAMP2 heterodimers are CGRP and adrenomedullin (AM) receptors, respectively, and the CLR associated with RAMP3 is a mixed type AM/CGRP receptor. CLR/RAMP2 and -3 heterodimers are low affinity intermedin receptors. The vital role of AM signaling in normal embryonic development of the blood and lymphatic vascular systems was revealed in CLR-, RAMP2- and AM-deficient mice that die between embryonic days 13.5 and 15.5. Reduced AM signaling in mice heterozygous for defective AM, CLR or RAMP2 alleles impaired fertility and the stress-protective actions of AM in the cardiovascular system. Conditional and tissue specific gene knock out strategies for individual or combined disruption of α- and β-CGRP and RAMP1 and -3 encoding gene structures are required to further define the biological relevance of α- and β-CGRP.

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Abbreviations

AM:

adrenomedullin

AMY:

amylin

CGRP:

calcitonin gene-related peptide

CLR:

calcitonin receptor-like receptor

CRSP:

calcitonin receptor-stimulating peptide

CT:

calcitonin

CTR:

calcitonin receptor

IMD:

intermedin

RAMP:

receptor-activity-modifying protein

SMαA:

smooth muscle α-actin

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Acknowledgments

This work was supported by the Swiss National Science Foundation, the University of Zurich, and the Schweizerische Verein Balgrist

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Authors and Affiliations

  1. Former Research Laboratory for Calcium Metabolism, Orthopedic University Hospital Balgrist, University of Zurich, 8008, Zurich, Switzerland

    Walter Born & Jan A. Fischer

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  1. Walter Born
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  2. Jan A. Fischer
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Correspondence to Walter Born .

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Editors and Affiliations

  1. School of Biological Sciences, University of Auckland, Symonds St. 9, Auckland , 1142, New Zealand

    Deborah L. Hay

  2. University of Auckland, Symonds Street 3A, Auckland, 1142, New Zealand

    Ian M. Dickerson

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Born, W., Fischer, J.A. (2010). The Calcitonin Peptide Family: What Can We Learn from Receptor Knock Out and Transgenic Mice. In: Hay, D., Dickerson, I. (eds) The calcitonin gene-related peptide family. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2909-6_5

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