Calcitonin and calcitonin receptor-like receptors

common themes with family B GPCRs?

James Barwell, Joseph J. Gingell, Harriet A. Watkins, Julia K. Archbold, David R. Poyner, Debbie L. Hay

Research output: Contribution to journalArticle

Abstract

The calcitonin receptor (CTR) and calcitonin receptor-like receptor (CLR) are two of the 15 human family B (or Secretin-like) GPCRs. CTR and CLR are of considerable biological interest as their pharmacology is moulded by interactions with receptor activity-modifying proteins. They also have therapeutic relevance for many conditions, such as osteoporosis, diabetes, obesity, lymphatic insufficiency, migraine and cardiovascular disease. In light of recent advances in understanding ligand docking and receptor activation in both the family as a whole and in CLR and CTR specifically, this review reflects how applicable general family B GPCR themes are to these two idiosyncratic receptors. We review the main functional domains of the receptors; the N-terminal extracellular domain, the juxtamembrane domain and ligand interface, the transmembrane domain and the intracellular C-terminal domain. Structural and functional findings from the CLR and CTR along with other family B GPCRs are critically appraised to gain insight into how these domains may function. The ability for CTR and CLR to interact with receptor activity-modifying proteins adds another level of sophistication to these receptor systems but means careful consideration is needed when trying to apply generic GPCR principles. This review encapsulates current thinking in the realm of family B GPCR research by highlighting both conflicting and recurring themes and how such findings relate to two unusual but important receptors, CTR and CLR.
Original languageEnglish
Pages (from-to)51-65
Number of pages15
JournalBritish Journal of Pharmacology
Volume166
Issue number1
Early online date10 Apr 2012
DOIs
Publication statusPublished - May 2012

Fingerprint

Calcitonin Receptor-Like Protein
Calcitonin Receptors
Calcitonin
Receptor Activity-Modifying Proteins
Ligands
Secretin
Lymphatic Diseases
Migraine Disorders
Osteoporosis
Cardiovascular Diseases
Obesity
Pharmacology
Research

Keywords

  • calcitonin
  • CGRP
  • adrenomedullin
  • amylin
  • helix-cap
  • receptor activation
  • domain
  • receptor activity-modifying protein
  • RAMP
  • GPCR
  • juxtamembrane domain

Cite this

Barwell, James ; Gingell, Joseph J. ; Watkins, Harriet A. ; Archbold, Julia K. ; Poyner, David R. ; Hay, Debbie L. / Calcitonin and calcitonin receptor-like receptors : common themes with family B GPCRs?. In: British Journal of Pharmacology. 2012 ; Vol. 166, No. 1. pp. 51-65.
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Calcitonin and calcitonin receptor-like receptors : common themes with family B GPCRs? / Barwell, James; Gingell, Joseph J.; Watkins, Harriet A.; Archbold, Julia K.; Poyner, David R.; Hay, Debbie L.

In: British Journal of Pharmacology, Vol. 166, No. 1, 05.2012, p. 51-65.

Research output: Contribution to journalArticle

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AU - Barwell, James

AU - Gingell, Joseph J.

AU - Watkins, Harriet A.

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