The C. elegans ric-3 gene is required for maturation of nicotinic acetylcholine receptors.
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.
Halevi
Sarah
S
Department of Physiology, Hebrew University--Hadassah Medical School, Jerusalem 91120, Israel.
McKay
Jim
J
Palfreyman
Mark
M
Yassin
Lina
L
Eshel
Margalit
M
Jorgensen
Erik
E
Treinin
Millet
M
D000109:Acetylcholine / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D016923:Cell Death; D029721:Drosophila Proteins / Q000737:chemistry; D004351:Drug Resistance; D017238:Genes, Helminth; D007978:Levamisole / Q000494:pharmacology; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D009865:Oocytes; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D021381:Protein Transport; D051381:Rats; D018079:Receptors, GABA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D009435:Synaptic Transmission / Q000502:physiology; D014982:Xenopus laevis; D064569:alpha7 Nicotinic Acetylcholine Receptor
D029742:Caenorhabditis elegans Proteins; C579165:Chrna7 protein, rat; C454142:DEG-3 protein, C elegans; D029721:Drosophila Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D011978:Receptors, Nicotinic; D011993:Recombinant Fusion Proteins; D064569:alpha7 Nicotinic Acetylcholine Receptor; C454141:ric-3 protein, C elegans; D007978:Levamisole; D000109:Acetylcholine