title: The A- and B-type muscarinic acetylcholine receptors from Drosophila melanogaster couple to different second messenger pathways.
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.
authors.affiliation: Center for Functional and Comparative Insect Genomics, Department of Biology, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen, Denmark.
authors.forename: Guilin R
authors.initials: GR
authors.lastname: Ren
authors.affiliation: Center for Functional and Comparative Insect Genomics, Department of Biology, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen, Denmark.
authors.forename: Jonas
authors.initials: J
authors.lastname: Folke
authors.affiliation: Center for Functional and Comparative Insect Genomics, Department of Biology, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen, Denmark.
authors.forename: Frank
authors.initials: F
authors.lastname: Hauser
authors.affiliation: Center for Functional and Comparative Insect Genomics, Department of Biology, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen, Denmark.
authors.forename: Shizhong
authors.initials: S
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Cornelis J P
authors.initials: CJ
authors.lastname: Grimmelikhuijzen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004331:Drosophila melanogaster; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000737:chemistry / Q000378:metabolism*; D015290:Second Messenger Systems; D017386:Sequence Homology, Amino Acid
chemical_list: D020033:Protein Isoforms; D011976:Receptors, Muscarinic
keywords: Acetylcholine; G protein-coupled receptor; GPCR; Hormone; Insect; Signaling