A mutated acetylcholine receptor subunit causes neuronal degeneration in C. elegans.

Neurotoxicity through abnormal activation of membrane channels is a potential cause of neurodegenerative disease. Here we show that a gain-of-function mutation, deg.3(u662), leads to the degeneration of a small set of neurons in the nematode C. elegans. The deg.3 gene encodes a nicotinic acetylcholine receptor alpha subunit, which in the region of transmembrane domain II is most similar to the neuronal alpha 7 subunits from rat and chicken. The u662 mutation changes a residue in the second transmembrane domain, the domain thought to form the channel pore. A similar change in the equivalent amino acid in the chick protein produces channels that desensitize slowly. Channel hyperactivity may underlie the degenerations seen in the C. elegans deg.3(u662) mutants, since antagonists of nicotinic acetylcholine receptors suppress the deg-3(u662) mutant phenotypes.

• Publication year

  1995

• Venue

  Neuron

• Publication date

  1995-04-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/0896-6273(95)90231-7PMID 7718248
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Principles of Neurology

  1996cited by this paper
• Epibatidine, a potent analgetic and nicotinic agonist.

  1994cited by this paper
• Green fluorescent protein as a marker for gene expression.

  1994cited by this paper
• The lung amiloride-sensitive Na+ channel: biophysical properties, pharmacology, ontogenesis, and molecular cloning.

  1994cited by this paper
• Gene interactions affecting mechanosensory transduction in Caenorhabditis elegans

  1994cited by this paper
• Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits

  1994cited by this paper
• Stratification of the channel domain in neurotransmitter receptors.

  1993cited by this paper
• Myasthenic Syndromes Attributed to Mutations Affecting the Epsilon Subunit of the Acetylcholine Receptor a

  1993cited by this paper
• Molecular cloning, functional properties, and distribution of rat brain alpha 7: a nicotinic cation channel highly permeable to calcium

  1993cited by this paper
• Combinatorial control of touch receptor neuron expression in Caenorhabditis elegans.

  1993cited by this paper
• Epithelial sodium channel related to proteins involved in neurodegeneration

  1993cited by this paper
• Expression cloning of an epithelial amiloride‐sensitive Na+ channel

  1993cited by this paper
• Mutations at two distinct sites within the channel domain M2 alter calcium permeability of neuronal alpha 7 nicotinic receptor.

  1993cited by this paper
• Operons in C. elegans: polycistronic mRNA precursors are processed by trans-splicing of SL2 to downstream coding regions.

  1993cited by this paper
• Diversity of nicotinic acetylcholine receptors in rat hippocampal neurons. I. Pharmacological and functional evidence for distinct structural subtypes.

  1993cited by this paper
• Opening the gates on ion channel diseases

  1992cited by this paper
• Mutations in the channel domain of a neuronal nicotinic receptor convert ion selectivity from cationic to anionic

  1992cited by this paper
• Cholinergic inhibition of short (outer) hair cells of the chick's cochlea

  1992cited by this paper
• Functional architecture of the nicotinic acetylcholine receptor: from electric organ to brain.

  1991cited by this paper
• The mec-4 gene is a member of a family of Caenorhabditis elegans genes that can mutate to induce neuronal degeneration

  1991cited by this paper
• Methyllycaconitine: a selective probe for neuronal alpha-bungarotoxin binding sites.

  1990cited by this paper
• The identification and suppression of inherited neurodegeneration in Caenorhabditis elegans

  1990cited by this paper
• Congenital Disorders of Neuromuscular Transmission

  1990cited by this paper
• A neuronal nicotinic acetylcholine receptor subunit (alpha 7) is developmentally regulated and forms a homo-oligomeric channel blocked by alpha-BTX.

  1990cited by this paper
• Methyllycaconitine: a selective probe for neuronal α‐bungarotoxin binding sites

  1990cited by this paper
• A second trans-spliced RNA leader sequence in the nematode Caenorhabditis elegans.

  1989cited by this paper
• Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists

  1988cited by this paper
• mec-3, a homeobox-containing gene that specifies differentiation of the touch receptor neurons in C. elegans.

  1988cited by this paper
• Nicotinic antagonists enhance process outgrowth by rat retinal ganglion cells in culture.

  1988cited by this paper
• A trans-spliced leader sequence on actin mRNA in C. elegans

  1987cited by this paper
• Activation of a transposable element in the germ line but not the soma of Caenorhabditis elegans

  1987cited by this paper
• Toward a physical map of the genome of the nematode Caenorhabditis elegans.

  1986cited by this paper
• The structure of the nervous system of the nematode Caenorhabditis elegans.

  1986cited by this paper
• Acetylcholine receptor binding site contains a disulfide cross-link between adjacent half-cystinyl residues.

  1986cited by this paper
• Molecular structure of the nicotinic acetylcholine receptor.

  1983cited by this paper
• Evidence for a transposon in Caenorhabditis elegans.

  1983cited by this paper
• Calcium-mediated myopathy at neuromuscular junctions of normal and dystrophic muscle.

  1982cited by this paper
• Developmental genetics of the mechanosensory neurons of Caenorhabditis elegans.

  1981cited by this paper
• unc-93(e1500): A behavioral mutant of Caenorhabditis elegans that defines a gene with a wild-type null phenotype.

  1980cited by this paper
• Levamisole-resistant mutants of the nematode Caenorhabditis elegans appear to lack pharmacological acetylcholine receptors.

  1980cited by this paper
• Agonist-induced myopathy at the neuromuscular junction is mediated by calcium

  1979cited by this paper
• Calcium dependence of toxic cell death: a final common pathway.

  1979cited by this paper
• Regulation of dopamine release by presynaptic nicotinic receptors in rat striatal slices: effect of nicotine in a low concentration.

  1979cited by this paper
• The genetics of Caenorhabditis elegans.

  1974cited by this paper

• Neurobiological and Neurophysiological Impacts of Real Spaceflight and Simulated Microgravity on C. elegans: A Comprehensive Review

  2025cites this paper
• The PVD neuron has male-specific structure and mating function in C. elegans

  2025cites this paper
• The PVD neuron has male-specific structure and mating function in Caenorhabditis elegans

  2025cites this paper
• How do necrotic cells expose phosphatidylserine to attract their predators—What’s unique and what’s in common with apoptotic cells

  2023cites this paper
• The diverse family of Cys-loop receptors in Caenorhabditis elegans: insights from electrophysiological studies

  2023cites this paper
• Exposure to 6-PPD Quinone at Environmentally Relevant Concentrations Causes Abnormal Locomotion Behaviors and Neurodegeneration in Caenorhabditis elegans.

  2023cites this paper
• Lysoptosis is an evolutionarily conserved cell death pathway moderated by intracellular serpins

  2022cites this paper
• Genetic Methods for Cellular Manipulation in C. elegans.

  2022cites this paper
• Assessment of Neuronal Cell Death in Caenorhabditis elegans.

  2022cites this paper
• Invited review: Unearthing the mechanisms of age-related neurodegenerative disease using Caenorhabditis elegans.

  2022cites this paper
• Neuron tracing and quantitative analyses of dendritic architecture reveal symmetrical three-way-junctions and phenotypes of git-1 in C. elegans

  2021cites this paper
• Advances in our understanding of nematode ion channels as potential anthelmintic targets

  2021cites this paper
• Cholinergic transmission in C. elegans: Functions, diversity, and maturation of ACh‐activated ion channels

  2020cites this paper
• Calcium ions trigger the exposure of phosphatidylserine on the surface of necrotic cells

  2020cites this paper
• Calcium ions trigger PS exposure on necrotic cells

  2020influential citation
• The Role of Ca2+ Signaling in Aging and Neurodegeneration: Insights from Caenorhabditis elegans Models

  2020cites this paper
• Adhesive L1CAM-Robo Signaling Aligns Growth Cone F-Actin Dynamics to Promote Axon-Dendrite Fasciculation in C. elegans.

  2019cites this paper
• Genetic analysis of KillerRed in C. elegans identifies a shared role of calcium genes in ROS-mediated neurodegeneration

  2018cites this paper
• Tobacco Smoking Addiction: Epidemiology, Genetics, Mechanisms, and Treatment

  2018cites this paper
• Evolutionary Relations of Genes Encoding Nicotinic Acetylcholine Receptor Subunits

  2018cites this paper
• EOR-1 mediates non-cell autonomous regulation of abts-1 gene expression in HSNs

  2018cites this paper
• Investigation of feeding behaviour in C. elegans reveals distinct pharmacological and antibacterial effects of nicotine

  2018cites this paper
• Distinct unfolded protein responses mitigate or mediate effects of nonlethal deprivation of C. elegans sleep in different tissues

  2017cites this paper
• Transcriptional control of non-apoptotic developmental cell death in C. elegans

  2016cites this paper
• Evolutionary Relationship of Nicotinic Acetylcholine Receptor Subunits in Both Vertebrate and Invertebrate Species

  2016cites this paper
• The Influence of the Transmembrane Protein EAT-18 upon Nicotinic Acetyicholine Receptors

  2016cites this paper
• Correction: Necrotic Cells Actively Attract Phagocytes through the Collaborative Action of Two Distinct PS-Exposure Mechanisms

  2015cites this paper
• Genetic Methods for Cellular Manipulations in C. elegans.

  2015cites this paper
• Components of the Ubiquitin Proteasome System are Required for the Nonapoptotic Death of the C. Elegans Linker Cell

  2015influential citation
• Necrotic Cells Actively Attract Phagocytes through the Collaborative Action of Two Distinct PS-Exposure Mechanisms

  2015cites this paper
• The levamisole sensitive nicotinic acetylcholine receptor of the potato cyst nematode Globodera pallida

  2015cites this paper
• How are necrotic cells recognized by their predators?

  2015cites this paper
• Examining the Neuroprotective Properties of 3-Dimethoxybenzylidene-Anabasine (DMXB-A) in a Third Trimester Chronic Ethanol Exposure Model in Rats

  2015cites this paper
• Erratum: Betaine acts on a ligand-gated ion channel in the nervous system of the nematode C. elegans

  2014cites this paper
• Caenorhabditis elegans nicotinic acetylcholine receptors are required for nociception

  2014influential citation
• Necrotic cell death in Caenorhabditis elegans.

  2014influential citation
• Noncanonical cell death in the nematode Caenorhabditis elegans.

  2014cites this paper
• Activity Regulates Neuronal Connectivity and Function in the C. elegans Motor Circuit: A Dissertation

  2014cites this paper
• Monitoring the clearance of apoptotic and necrotic cells in the nematode Caenorhabditis elegans.

  2013cites this paper
• Betaine acts on a ligand-gated ion channel in the nervous system of the nematode C. elegans

  2013cites this paper
• The Caenorhabditis elegans interneuron ALA is (also) a high-threshold mechanosensor

  2013cites this paper
• Roles of nicotinic acetylcholine receptors in stem cell survival/apoptosis, proliferation and differentiation.

  2013cites this paper
• Use of the Operon Structure of the C. elegans Genome as a Tool to Identify Functionally Related Proteins

  2013cites this paper
• Cholinergic modulation of cognitive processing: insights drawn from computational models

  2012cites this paper
• Parasitic nematode ion channels : improving understanding of pharmacology and genetic composition

  2012cites this paper
• Maintaining the Balance: Coordinating Excitation and Inhibition in a Simple Motor Circuit: A Dissertation

  2012cites this paper
• Axon regeneration pathways identified by systematic genetic screening in C. elegans.

  2011cites this paper
• Axon response to guidance cues is stimulated by acetylcholine in C . elegans

  2011cites this paper
• elegans Notch Signaling Regulates Adult Chemosensory Response and Larval Molting Quiescence

  2011cites this paper
• C. elegans multi-dendritic sensory neurons: morphology and function.

  2011influential citation
• Shared gene expression in distinct neurons expressing common selector genes

  2011cites this paper
• Axon Response to Guidance Cues Is Stimulated by Acetylcholine in Caenorhabditis elegans

  2011cites this paper
• Ion channels and receptor as targets for the control of parasitic nematodes.

  2011cites this paper
• Endocytosis and intracellular trafficking contribute to necrotic neurodegeneration in C. elegans

  2011cites this paper
• Characterization of caspase regulation and Hepatitis B Virus induced cell death in the nematode Caenorhabditis elegans

  2011cites this paper
• Reporter Mutation Studies Show That Nicotinic Acetylcholine Receptor (nAChR) α5 Subunits and/or Variants Modulate Function of α6*-nAChR*

  2011cites this paper
• Naturally-expressed nicotinic acetylcholine receptor subtypes.

  2011cites this paper
• GABAergic Synaptic Plasticity during a Developmentally Regulated Sleep-Like State in C. elegans

  2011cites this paper
• INVESTIGATION OF THE EFFECTS OF NICOTINE AND LEVAMISOLE ON SW620 COLON ADENOCARCINOMA CELLS USING A CUSTOMIZED R-ROUTINE FOR AUTOMATED MICROARRAY ANALYSIS

  2010cites this paper
• Medium- and high-throughput screening of neurotoxicants using C. elegans.

  2010cites this paper
• A Dominant Mutation in a Neuronal Acetylcholine Receptor Subunit Leads to Motor Neuron Degeneration in Caenorhabditis elegans

  2010cites this paper
• Non‐apoptotic cell death in Caenorhabditis elegans

  2010cites this paper
• Alteration of the nuclear pore complex in Ca2+-mediated cell death

  2010cites this paper
• Paired and LIM class homeodomain proteins coordinate differentiation of the C. elegans ALA neuron

  2010cites this paper
• Investigation of the effects of nicotine and levamisole on SW620 colon adenocarcinoma cells using a customized r-routine for automated microarray analysis

  2010cites this paper
• A Neuronal Acetylcholine Receptor Regulates the Balance of Muscle Excitation and Inhibition in Caenorhabditis elegans

  2009cites this paper
• Autophagy in C. elegans.

  2009cites this paper
• The BTB-MATH protein BATH-42 interacts with RIC-3 to regulate maturation of nicotinic acetylcholine receptors

  2009cites this paper
• A review of experimental techniques used for the heterologous expression of nicotinic acetylcholine receptors.

  2009cites this paper
• The genetics of the sexually dimorphic deaths of the C. elegans CEM neutrons

  2009cites this paper
• Molecular and genetic dissection of neuronal necrotic-like death in Caenorhabditis elegans

  2009influential citation
• The cell biology of autophagy in metazoans: a developing story

  2008cites this paper
• Noncanonical cell death programs in the nematode Caenorhabditis elegans

  2008cites this paper
• Autophagy and cell death in Caenorhabditis elegans.

  2008cites this paper
• RIC‐3: a nicotinic acetylcholine receptor chaperone

  2008cites this paper
• Activation of Alpha7 Subunit Containing Nicotinic Acetylcholine Receptors Mediates Cell Death of Neurons in the Avian Ciliary Ganglion

  2008influential citation
• The varitint-waddler (Va) deafness mutation in TRPML3 generates constitutive, inward rectifying currents and causes cell degeneration

  2008cites this paper
• Doktori értekezés-vegleges

  2008cites this paper
• Caenorhabditis elegans Genes Required for the Engulfment of Apoptotic Corpses Function in the Cytotoxic Cell Deaths Induced by Mutations in lin-24 and lin-33

  2008cites this paper
• Alpha 7 nicotinic acetylcholine receptors: Molecular pharmacology and role in neuroprotection

  2008cites this paper
• Non-developmentally programmed cell death in Caenorhabditis elegans.

  2007cites this paper
• Acetylcholine.

  2007cites this paper
• Epidermal growth factor signaling induces behavioral quiescence in Caenorhabditis elegans

  2007cites this paper
• The frataxin-encoding operon of Caenorhabditis elegans shows complex structure and regulation.

  2007cites this paper
• Guidelines on nicotine dose selection for in vivo research

  2007cites this paper
• Using Caenorhabditis elegans models of neurodegenerative disease to identify neuroprotective strategies.

  2007cites this paper
• Influence of autophagy genes on ion-channel-dependent neuronal degeneration in Caenorhabditis elegans

  2007cites this paper
• The cys-loop ligand-gated ion channel gene family of Brugia malayi and Trichinella spiralis: a comparison with Caenorhabditis elegans

  2007cites this paper
• Cell-Autonomous Inhibition of α7-Containing Nicotinic Acetylcholine Receptors Prevents Death of Parasympathetic Neurons during Development

  2007cites this paper
• The regulation of programmed and pathological cell death in C. elegans

  2006cites this paper
• Evidence for a Diverse Cys-Loop Ligand-Gated Ion Channel Superfamily in Early Bilateria

  2006cites this paper
• Neuronal nicotinic acetylcholine receptors serve as sensitive targets that mediate β-amyloid neurotoxicity

  2006cites this paper
• The chemosensory system of Caenorhabditis elegans and other nematodes

  2006cites this paper
• Necrotic death as a cell fate.

  2006cites this paper
• Are there non-catalytic functions of acetylcholinesterases? Lessons from mutant animal models.

  2005cites this paper
• Proteolytic mechanisms in necrotic cell death and neurodegeneration

  2005cites this paper
• The vacuolar H+ -ATPase mediates intracellular acidification required for neurodegeneration in C. elegans.

  2005cites this paper
• Temporal-Spatial Expression and Transcriptional Regulation of α7 Nicotinic Acetylcholine Receptor by Thyroid Transcription Factor-1 and Early Growth Response Factor-1 during Murine Lung Development*

  2005cites this paper
• The use of Caenorhabditis elegans in molecular neuropharmacology.

  2004cites this paper
• Genetic dissection of an acetylcholine receptor involved in neuronal degeneration

  2004cites this paper