Edit, cut and paste in the nicotinic acetylcholine receptor gene family of Drosophila melanogaster.
Nicotinic acetylcholine receptors (nAChRs) are important for fast synaptic cholinergic transmission. They are targets of drugs/chemicals for human and animal health as well as for pest control. With the advent of genome sequencing, entire nAChR gene families have now been described for vertebrates and invertebrates. Mostly, these are extensive with a large number of distinct subunits, making possible many nAChR subtypes differing in transmitter affinity, channel conductance, ion selectivity, desensitization, modulation and pharmacology. The smallest nAChR gene family to date is that of the fruit fly, Drosophila melanogaster, with only 10 members. This apparently compact family belies its true diversity as 4 of the 10 subunits show alternative splicing. Also, using Drosophila, A-to-I pre-mRNA editing has been demonstrated for the first time in nAChRs. Such is the extent of this variation, that one subunit alone (Dalpha6) can potentially generate far more isoforms than seen in entire gene families from other species. We present here three-dimensional models constructed for insect nAChRs, which show that many variations introduced by alternative splicing and RNA editing may influence receptor function.
Sattelle
D B
DB
MRC Functional Genetics Unit, Department of Human Anatomy & Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK. david.sattelle@human-anatomy.oxford.ac.uk
Jones
A K
AK
Sattelle
B M
BM
Matsuda
K
K
Reenan
R
R
Biggin
P C
PC
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018678:Cholinergic Agents / Q000737:chemistry / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism; D007306:Insecticides / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D000073943:Neonicotinoids; D009574:Nitro Compounds; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D017393:RNA Editing; D012323:RNA Processing, Post-Transcriptional; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment
D018678:Cholinergic Agents; D007093:Imidazoles; D007306:Insecticides; D000073943:Neonicotinoids; D009574:Nitro Compounds; D020033:Protein Isoforms; D021122:Protein Subunits; D011978:Receptors, Nicotinic; C082359:imidacloprid