Abstract
Nicotinic (cholinergic) neurotransmission plays a critical role in the vertebrate nervous system, underlies nicotine addiction, and nicotinic receptor dysfunction leads to neurological disorders. The C. elegans neuromuscular junction (NMJ) shares many characteristics with neuronal synapses, including multiple classes of postsynaptic currents. Here, we identify two genes required for the major excitatory current found at the C. elegans NMJ: acr-16, which encodes a nicotinic AChR subunit homologous to the vertebrate alpha7 subunit, and cam-1, which encodes a Ror receptor tyrosine kinase. acr-16 mutants lack fast cholinergic current at the NMJ and exhibit synthetic behavioral deficits with other known AChR mutants. In cam-1 mutants, ACR-16 is mislocalized and ACR-16-dependent currents are disrupted. The postsynaptic deficit in cam-1 mutants is accompanied by alterations in the distribution of cholinergic vesicles and associated synaptic proteins. We hypothesize that CAM-1 contributes to the localization or stabilization of postsynaptic ACR-16 receptors and presynaptic release sites.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylcholine / metabolism
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Acetylcholine / pharmacology
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Analysis of Variance
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Animals
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Animals, Genetically Modified
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Behavior, Animal
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Caenorhabditis elegans
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Caenorhabditis elegans Proteins / classification
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / physiology*
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Calcium / metabolism
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Choline / pharmacology
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Cholinergic Antagonists / pharmacology
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Diagnostic Imaging
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Dihydro-beta-Erythroidine / pharmacology
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Electric Stimulation / methods
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Gene Expression Regulation / genetics
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In Vitro Techniques
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Ion Channel Gating / drug effects
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Ion Channel Gating / physiology
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Levamisole / pharmacology
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Membrane Potentials / drug effects
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Membrane Potentials / genetics
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Membrane Potentials / radiation effects
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Microscopy, Electron, Transmission / methods
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Molecular Biology
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Movement / physiology
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Muscles / drug effects
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Muscles / physiology
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Mutagenesis
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Mutation
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Neuromuscular Junction / drug effects
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Neuromuscular Junction / metabolism*
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Neurons / physiology
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Nicotine / pharmacology
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Patch-Clamp Techniques / methods
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RNA, Small Interfering
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Receptor Protein-Tyrosine Kinases / physiology*
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Receptor Tyrosine Kinase-like Orphan Receptors
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Receptors, Nicotinic / physiology*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology*
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Synaptic Vesicles / metabolism
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Synaptic Vesicles / ultrastructure
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Time Factors
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Trans-Activators / pharmacology
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gamma-Aminobutyric Acid / metabolism
Substances
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Caenorhabditis elegans Proteins
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Cholinergic Antagonists
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RNA, Small Interfering
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Receptors, Nicotinic
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Trans-Activators
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acr-16 protein, C elegans
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Dihydro-beta-Erythroidine
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Levamisole
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gamma-Aminobutyric Acid
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Nicotine
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CAM-1 protein, C elegans
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Receptor Protein-Tyrosine Kinases
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Receptor Tyrosine Kinase-like Orphan Receptors
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Choline
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Acetylcholine
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Calcium