Differential coupling of the extreme C-terminus of G protein alpha subunits to the G protein-coupled melatonin receptors

Janice Drew, Perry Barrett, S Conway, P Delagrange, Peter John Morgan

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Melatonin receptors interact with pertussis toxin-sensitive G proteins to inhibit adenylate cyclase. However, the G protein coupling profiles of melatonin receptor subtypes have not been fully characterised and alternative G protein coupling is evident. The five C-terminal residues of Galpha subunits confer coupling specificity to G protein-coupled receptors. This report outlines the use of Gas chimaeras to alter the signal output of human melatonin receptors and investigate their interaction with the C-termini of Get subunits. The Gas portion of the chimaeras confers the ability to activate adenylate cyclase leading to cyclic AMP production. Co-transfection of HEK293 cells expressing MT1, or MT2 melatonin receptors with Gas chimaeras and a cyclic AMP activated luciferase construct provided a convenient and sensitive assay system for identification of receptor recognition of Ga C-termini. Luciferase assay sensitivity was compared with measurement of cyclic AMP elevations by radioimmunoassay. Differential interactions of the melatonin receptor subtypes with Ga chimaeras were observed. Temporal and kinetic parameters of cyclic AMP responses measured by cyclic AMP radioimmunoassay varied depending on the Gas chimaeras coupled. Recognition of the C-terminal five amino acids of the Ga subunit is a requisite for coupling to a receptor, but it is not the sole determinant. (C) 2002 Elsevier Science B.V. All rights reserved.

Original languageEnglish
Pages (from-to)185-192
Number of pages8
JournalBiochimica et Biophysica Acta. Molecular Cell Research
Issue number2
Early online date16 Sept 2002
Publication statusPublished - 21 Oct 2002


  • melatonin receptor
  • G protein-coupled receptor
  • G alpha chimaera
  • xenopus dermal melanophores
  • ovine pars tuberalis
  • 2-<I-125>iodomelatonin binding
  • signal-transduction
  • ligand-binding
  • identification
  • activation
  • expression
  • residues
  • MEL1A


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