Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Fleming JT, Squire MD, Barnes TM, Tornoe C, Matsuda K, Ahnn J, Fire A, Sulston JE, Barnard EA, Sattelle DB, Lewis JA.
???displayArticle.abstract???
We show that three of the eleven genes of the nematode Caenorhabditis elegans that mediate resistance to the nematocide levamisole and to other cholinergic agonists encode nicotinic acetylcholine receptor (nAChR) subunits. unc-38 encodes an alpha subunit while lev-1 and unc-29 encode non-alpha subunits. The nematode nAChR subunits show conservation of many mammalian nAChR sequence features, implying an ancient evolutionary origin of nAChR proteins. Expression in Xenopus oocytes of combinations of these subunits that include the unc-38 alpha subunit results in levamisole-induced currents that are suppressed by the nAChR antagonists mecamylamine, neosurugatoxin, and d-tubocurarine but not alpha-bungarotoxin. The mutant phenotypes reveal that unc-38 and unc-29 subunits are necessary for nAChR function, whereas the lev-1 subunit is not. An UNC-29-GFP fusion shows that UNC-29 is expressed in body and head muscles. Two dominant mutations of lev-1 result in a single amino acid substitution or addition in or near transmembrane domain 2, a region important to ion channel conductance and desensitization. The identification of viable nAChR mutants in C. elegans provides an advantageous system in which receptor expression and synaptic targeting can be manipulated and studied in vivo.
Abramson,
An analog of lophotoxin reacts covalently with Tyr190 in the alpha-subunit of the nicotinic acetylcholine receptor.
1989, Pubmed
Abramson,
An analog of lophotoxin reacts covalently with Tyr190 in the alpha-subunit of the nicotinic acetylcholine receptor.
1989,
Pubmed Abramson,
Lophotoxin and related coral toxins covalently label the alpha-subunit of the nicotinic acetylcholine receptor.
1988,
Pubmed Ajuh,
Cloning of a cDNA encoding a putative nicotinic acetylcholine receptor subunit of the human filarial parasite Onchocerca volvulus.
1994,
Pubmed Alfonso,
Cloning and characterization of the choline acetyltransferase structural gene (cha-1) from C. elegans.
1994,
Pubmed Arpagaus,
cDNA sequence, gene structure, and in vitro expression of ace-1, the gene encoding acetylcholinesterase of class A in the nematode Caenorhabditis elegans.
1994,
Pubmed Bai,
Actions of a coral toxin analogue (bipinnatin-B) on an insect nicotinic acetylcholine receptor.
1993,
Pubmed Ballivet,
Nicotinic acetylcholine receptors in the nematode Caenorhabditis elegans.
1996,
Pubmed
,
Xenbase Barchan,
How the mongoose can fight the snake: the binding site of the mongoose acetylcholine receptor.
1992,
Pubmed Bargmann,
Laser killing of cells in Caenorhabditis elegans.
1995,
Pubmed Barnard,
Receptor classes and the transmitter-gated ion channels.
1992,
Pubmed Barnes,
Echolocation: a PCR-based strategy for reliably and rapidly mapping transposon insertion sites.
1990,
Pubmed Baylis,
ACR-3, a Caenorhabditis elegans nicotinic acetylcholine receptor subunit. Molecular cloning and functional expression.
1997,
Pubmed
,
Xenbase Bossy,
Conservation of neural nicotinic acetylcholine receptors from Drosophila to vertebrate central nervous systems.
1988,
Pubmed Brenner,
The genetics of Caenorhabditis elegans.
1974,
Pubmed Buonanno,
Isolation and characterization of the beta and epsilon subunit genes of mouse muscle acetylcholine receptor.
1989,
Pubmed Chalfie,
Green fluorescent protein as a marker for gene expression.
1994,
Pubmed Chomczynski,
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
1987,
Pubmed Claudio,
Fibroblasts transfected with Torpedo acetylcholine receptor beta-, gamma-, and delta-subunit cDNAs express functional receptors when infected with a retroviral alpha recombinant.
1989,
Pubmed Collins,
Activation of a transposable element in the germ line but not the soma of Caenorhabditis elegans.
,
Pubmed Coulson,
Toward a physical map of the genome of the nematode Caenorhabditis elegans.
1986,
Pubmed Couturier,
A neuronal nicotinic acetylcholine receptor subunit (alpha 7) is developmentally regulated and forms a homo-oligomeric channel blocked by alpha-BTX.
1990,
Pubmed
,
Xenbase Czajkowski,
Negatively charged amino acid residues in the nicotinic receptor delta subunit that contribute to the binding of acetylcholine.
1993,
Pubmed
,
Xenbase Dascal,
Xenopus oocyte resting potential, muscarinic responses and the role of calcium and guanosine 3',5'-cyclic monophosphate.
1984,
Pubmed
,
Xenbase Devillers-Thiéry,
Functional architecture of the nicotinic acetylcholine receptor: a prototype of ligand-gated ion channels.
1993,
Pubmed Felsenstein,
Estimating effective population size from samples of sequences: a bootstrap Monte Carlo integration method.
1992,
Pubmed Fire,
Integrative transformation of Caenorhabditis elegans.
1986,
Pubmed Fleming,
Acetylcholine receptor molecules of the nematode Caenorhabditis elegans.
1993,
Pubmed Frohman,
Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer.
1988,
Pubmed Galzi,
Mutations in the channel domain of a neuronal nicotinic receptor convert ion selectivity from cationic to anionic.
1992,
Pubmed
,
Xenbase Gautam,
Defective neuromuscular synaptogenesis in agrin-deficient mutant mice.
1996,
Pubmed Gautam,
Failure of postsynaptic specialization to develop at neuromuscular junctions of rapsyn-deficient mice.
1995,
Pubmed Godzik,
Conservation of residue interactions in a family of Ca-binding proteins.
1989,
Pubmed Greenwald,
lin-12, a nematode homeotic gene, is homologous to a set of mammalian proteins that includes epidermal growth factor.
1985,
Pubmed Heim,
Wavelength mutations and posttranslational autoxidation of green fluorescent protein.
1994,
Pubmed Hermans-Borgmeyer,
Primary structure of a developmentally regulated nicotinic acetylcholine receptor protein from Drosophila.
1986,
Pubmed Higgins,
CLUSTAL V: improved software for multiple sequence alignment.
1992,
Pubmed Huganir,
Phosphorylation of the nicotinic acetylcholine receptor by an endogenous tyrosine-specific protein kinase.
1984,
Pubmed Huganir,
cAMP-dependent protein kinase phosphorylates the nicotinic acetylcholine receptor.
1983,
Pubmed Imoto,
Rings of negatively charged amino acids determine the acetylcholine receptor channel conductance.
1988,
Pubmed
,
Xenbase Jacobson,
Purification and fractionation of poly(A)+ RNA.
1987,
Pubmed Jin,
Control of type-D GABAergic neuron differentiation by C. elegans UNC-30 homeodomain protein.
,
Pubmed Kao,
Acetylcholine receptor binding site contains a disulfide cross-link between adjacent half-cystinyl residues.
1986,
Pubmed Karlin,
Structure of nicotinic acetylcholine receptors.
1993,
Pubmed Karlin,
Toward a structural basis for the function of nicotinic acetylcholine receptors and their cousins.
1995,
Pubmed Konno,
Rings of anionic amino acids as structural determinants of ion selectivity in the acetylcholine receptor channel.
1991,
Pubmed
,
Xenbase Krause,
A trans-spliced leader sequence on actin mRNA in C. elegans.
1987,
Pubmed Lewis,
Cholinergic receptor mutants of the nematode Caenorhabditis elegans.
1987,
Pubmed Lewis,
The levamisole receptor, a cholinergic receptor of the nematode Caenorhabditis elegans.
1987,
Pubmed Lewis,
The genetics of levamisole resistance in the nematode Caenorhabditis elegans.
1980,
Pubmed Lewis,
Levamisole-resistant mutants of the nematode Caenorhabditis elegans appear to lack pharmacological acetylcholine receptors.
1980,
Pubmed Marshall,
Sequence and functional expression of a single alpha subunit of an insect nicotinic acetylcholine receptor.
1990,
Pubmed
,
Xenbase Martin,
The physiology and pharmacology of neuromuscular transmission in the nematode parasite, Ascaris suum.
1991,
Pubmed Mello,
DNA transformation.
1995,
Pubmed Mello,
Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences.
1991,
Pubmed Miller,
A genetic selection for Caenorhabditis elegans synaptic transmission mutants.
1996,
Pubmed Miller,
Mosaic analysis using a ncl-1 (+) extrachromosomal array reveals that lin-31 acts in the Pn.p cells during Caenorhabditis elegans vulval development.
1996,
Pubmed Moerman,
Molecular cloning of the muscle gene unc-22 in Caenorhabditis elegans by Tc1 transposon tagging.
1986,
Pubmed Moerman,
Spontaneous unstable unc-22 IV mutations in C. elegans var. Bergerac.
1984,
Pubmed Moerman,
Identification and intracellular localization of the unc-22 gene product of Caenorhabditis elegans.
1988,
Pubmed Nef,
Genes expressed in the brain define three distinct neuronal nicotinic acetylcholine receptors.
1988,
Pubmed Nef,
Structure linkage, and sequence of the two genes encoding the delta and gamma subunits of the nicotinic acetylcholine receptor.
1984,
Pubmed Neumann,
Snake acetylcholine receptor: cloning of the domain containing the four extracellular cysteines of the alpha subunit.
1989,
Pubmed Nonet,
Synaptic function is impaired but not eliminated in C. elegans mutants lacking synaptotagmin.
1993,
Pubmed Okkema,
Sequence requirements for myosin gene expression and regulation in Caenorhabditis elegans.
1993,
Pubmed Ortells,
Evolutionary history of the ligand-gated ion-channel superfamily of receptors.
1995,
Pubmed Pedersen,
d-Tubocurarine binding sites are located at alpha-gamma and alpha-delta subunit interfaces of the nicotinic acetylcholine receptor.
1990,
Pubmed Revah,
Mutations in the channel domain alter desensitization of a neuronal nicotinic receptor.
1991,
Pubmed
,
Xenbase Robertson,
Levamisole-activated single-channel currents from muscle of the nematode parasite Ascaris suum.
1993,
Pubmed Saitou,
The neighbor-joining method: a new method for reconstructing phylogenetic trees.
1987,
Pubmed Sargent,
The diversity of neuronal nicotinic acetylcholine receptors.
1993,
Pubmed Schuler,
A workbench for multiple alignment construction and analysis.
1991,
Pubmed Squire,
Molecular cloning and functional co-expression of a Caenorhabditis elegans nicotinic acetylcholine receptor subunit (acr-2).
1995,
Pubmed
,
Xenbase Thompson,
CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice.
1994,
Pubmed Tornøe,
Actions of neurotoxins (bungarotoxins, neosurugatoxin and lophotoxins) on insect and nematode nicotinic acetylcholine receptors.
1995,
Pubmed Treinin,
A mutated acetylcholine receptor subunit causes neuronal degeneration in C. elegans.
1995,
Pubmed Unwin,
Acetylcholine receptor channel imaged in the open state.
1995,
Pubmed Unwin,
Neurotransmitter action: opening of ligand-gated ion channels.
1993,
Pubmed Unwin,
Nicotinic acetylcholine receptor at 9 A resolution.
1993,
Pubmed Unwin,
The structure of ion channels in membranes of excitable cells.
1989,
Pubmed Wiley,
Cloning and sequence analysis of the candidate nicotinic acetylcholine receptor alpha subunit gene tar-1 from Trichostrongylus colubriformis.
1996,
Pubmed Williams,
A genetic mapping system in Caenorhabditis elegans based on polymorphic sequence-tagged sites.
1992,
Pubmed Williams,
Genes critical for muscle development and function in Caenorhabditis elegans identified through lethal mutations.
1994,
Pubmed Yuan,
The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme.
1993,
Pubmed Zorio,
Operons as a common form of chromosomal organization in C. elegans.
1994,
Pubmed
