title: Two types of muscarinic acetylcholine receptors in Drosophila and other arthropods.
abstract: Muscarinic acetylcholine receptors (mAChRs) play a central role in the mammalian nervous system. These receptors are G protein-coupled receptors (GPCRs), which are activated by the agonists acetylcholine and muscarine, and blocked by a variety of antagonists. Mammals have five mAChRs (m1-m5). In this study, we cloned two structurally related GPCRs from the fruit fly Drosophila melanogaster, which, after expression in Chinese hamster ovary cells, proved to be muscarinic acetylcholine receptors. One mAChR (the A-type; encoded by gene CG4356) is activated by acetylcholine (EC50, 5 × 10(-8) M) and muscarine (EC50, 6 × 10(-8) M) and blocked by the classical mAChR antagonists atropine, scopolamine, and 3-quinuclidinyl-benzilate (QNB), while the other (the B-type; encoded by gene CG7918) is also activated by acetylcholine, but has a 1,000-fold lower sensitivity to muscarine, and is not blocked by the antagonists. A- and B-type mAChRs were also cloned and functionally characterized from the red flour beetle Tribolium castaneum. Recently, Haga et al. (Nature 2012, 482: 547-551) published the crystal structure of the human m2 mAChR, revealing 14 amino acid residues forming the binding pocket for QNB. These residues are identical between the human m2 and the D. melanogaster and T. castaneum A-type mAChRs, while many of them are different between the human m2 and the B-type receptors. Using bioinformatics, one orthologue of the A-type and one of the B-type mAChRs could also be found in all other arthropods with a sequenced genome. Protostomes, such as arthropods, and deuterostomes, such as mammals and other vertebrates, belong to two evolutionarily distinct lineages of animal evolution that split about 700 million years ago. We found that animals that originated before this split, such as cnidarians (Hydra), had two A-type mAChRs. From these data we propose a model for the evolution of mAChRs.
authors.affiliation: Center for Functional and Comparative Insect Genomics, Department of Biology, University of Copenhagen, Universitetsparken 15, 2100, Copenhagen, Denmark.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Collin
authors.forename: Frank
authors.initials: F
authors.lastname: Hauser
authors.forename: Ernesto
authors.initials: E
authors.lastname: Gonzalez de Valdivia
authors.forename: Ernesto Gonzalez
authors.initials: EG
authors.lastname: de Valdivia
authors.forename: Shizhong
authors.initials: S
authors.lastname: Li
authors.forename: Julia
authors.initials: J
authors.lastname: Reisenberger
authors.forename: Eva M M
authors.initials: EM
authors.lastname: Carlsen
authors.forename: Zaid
authors.initials: Z
authors.lastname: Khan
authors.forename: Niels O
authors.initials: NO
authors.lastname: Hansen
authors.forename: Florian
authors.initials: F
authors.lastname: Puhm
authors.forename: Leif
authors.initials: L
authors.lastname: Søndergaard
authors.forename: Justyna
authors.initials: J
authors.lastname: Niemiec
authors.forename: Magdalena
authors.initials: M
authors.lastname: Heninger
authors.forename: Guilin R
authors.initials: GR
authors.lastname: Ren
authors.forename: Cornelis J P
authors.initials: CJ
authors.lastname: Grimmelikhuijzen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001181:Arthropods / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015536:Down-Regulation; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D011976:Receptors, Muscarinic / Q000235:genetics* / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D011976:Receptors, Muscarinic