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Biochem Biophys Res Commun. 2015 Jul 10;462(4):358-64. doi: 10.1016/j.bbrc.2015.04.141. Epub 2015 May 9.

The A- and B-type muscarinic acetylcholine receptors from Drosophila melanogaster couple to different second messenger pathways.

Author information

1
Center for Functional and Comparative Insect Genomics, Department of Biology, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen, Denmark.
2
Center for Functional and Comparative Insect Genomics, Department of Biology, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen, Denmark. Electronic address: cgrimmelikhuijzen@bio.ku.dk.

Abstract

Muscarinic acetylcholine receptors (mAChRs) are G protein-coupled receptors (GPCRs) that are activated by the agonists acetylcholine and muscarine and blocked by several antagonists, among them atropine. In mammals five mAChRs (m1-m5) exist of which m1, m3, and m5 are coupled to members of the Gq/11 family and m2 and m4 to members of the Gi/0 family. We have recently shown that Drosophila melanogaster and other arthropods have two mAChRs, named A and B, where the A-type has the same pharmacology as the mammalian mAChRs, while the B-type has a very low affinity to muscarine and no affinity to classical antagonists such as atropine. Here, we find that the D. melanogaster A-type mAChR is coupled to Gq/11 and D. melanogaster B-type mAChR to Gi/0. Furthermore, by comparing the second and third intracellular loops of all animal mAChRs for which the G protein coupling has been established, we could identify several amino acid residues likely to be specific for either Gq/11 or Gi/0 coupling. Using these hallmarks for specific mAChR G protein interaction we found that all protostomes with a sequenced genome have one mAChR coupled to Gq/11 and one to four mAChRs coupled to Gi/0. Furthermore, in protostomes, probably all A-type mAChRs are coupled to Gq/11 and all B-type mAChRs to G0/i.

KEYWORDS:

Acetylcholine; G protein-coupled receptor; GPCR; Hormone; Insect; Signaling

PMID:
25964087
DOI:
10.1016/j.bbrc.2015.04.141
[Indexed for MEDLINE]

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