Abstract
Mutations in ric-3 (resistant to inhibitors of cholinesterase) suppress the neuronal degenerations caused by a gain of function mutation in the Caenorhabditis elegans DEG-3 acetylcholine receptor. RIC-3 is a novel protein with two transmembrane domains and extensive coiled-coil domains. It is expressed in both muscles and neurons, and the protein is concentrated within the cell bodies. We demonstrate that RIC-3 is required for the function of at least four nicotinic acetylcholine receptors. However, GABA and glutamate receptors expressed in the same cells are unaffected. In ric-3 mutants, the DEG-3 receptor accumulates in the cell body instead of in the cell processes. Moreover, co-expression of ric-3 in Xenopus laevis oocytes enhances the activity of the C.elegans DEG-3/DES-2 and of the rat alpha-7 acetylcholine receptors. Together, these data suggest that RIC-3 is specifically required for the maturation of acetylcholine receptors.
Publication types
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Comparative Study
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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.
MeSH terms
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Acetylcholine / pharmacology
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Amino Acid Sequence
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Animals
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Caenorhabditis elegans / genetics*
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Caenorhabditis elegans / metabolism
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Caenorhabditis elegans Proteins / chemistry
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Caenorhabditis elegans Proteins / genetics*
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Caenorhabditis elegans Proteins / physiology*
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Cell Death
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Drosophila Proteins / chemistry
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Drug Resistance
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Genes, Helminth*
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Levamisole / pharmacology
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Molecular Sequence Data
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Muscle Proteins / chemistry
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Muscle Proteins / genetics
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Muscle Proteins / physiology*
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / physiology*
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Neurons / metabolism
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Oocytes
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Protein Structure, Tertiary
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Protein Subunits
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Protein Transport
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Rats
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Receptors, GABA / metabolism
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Receptors, Glutamate / metabolism
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Receptors, Nicotinic / genetics*
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Receptors, Nicotinic / physiology*
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Recombinant Fusion Proteins / physiology
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Sequence Alignment
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Sequence Homology, Amino Acid
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Synaptic Transmission / physiology
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Xenopus laevis
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alpha7 Nicotinic Acetylcholine Receptor
Substances
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Caenorhabditis elegans Proteins
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Chrna7 protein, rat
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DEG-3 protein, C elegans
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Drosophila Proteins
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Muscle Proteins
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Nerve Tissue Proteins
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Protein Subunits
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Receptors, GABA
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Receptors, Glutamate
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Receptors, Nicotinic
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Recombinant Fusion Proteins
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alpha7 Nicotinic Acetylcholine Receptor
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ric-3 protein, C elegans
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Levamisole
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Acetylcholine