Neuronal toxicity in Caenorhabditis elegans from an editing site mutant in glutamate receptor channels

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Rachel AronoffP H Seeburg

Abstract

Ionotropic glutamate receptors (iGluRs) in Caenorhabditis elegans are predicted to have high permeability for Ca2+ because of glutamine (Q) residues in the pore loop. This contrasts to the low Ca2+ permeability of similar iGluRs in principal neurons of mammals, because of an edited arginine (R) at the critical pore position in at least one channel subunit. Here, we introduced the R residue into the pore loop of a glutamate receptor subunit, GLR-2, in C. elegans. GLR-2(R) participated in channel formation, as revealed by decreased rectification of kainate-evoked currents in electrophysiological recordings when GLR-2(R) and the wild-type GLR-2(Q) were coexpressed in worms. Notably, the transgenic worms exhibited, at low penetrance, strong phenotypic impairments including uncoordination, neuronal degeneration, developmental arrest, and lethality. Penetrance of adverse phenotypes could be enhanced by transgenic expression of an optimal GLR-2(Q)/(R) ratio, implicating channel activity as the cause. In direct support, a mutation in eat-4, which prevents glutamatergic transmission, suppressed adverse phenotypes. Suppression was also achieved by mutation in calreticulin, which is necessary for maintainance of intracellular Ca2+ stores ...Continue Reading

Citations

Jul 19, 2005·Annual Review of Neuroscience·Mario de Bono, Andres Villu Maricq
Sep 21, 2013·G3 : Genes - Genomes - Genetics·Osama RefaiJeb Gaudet
Jan 1, 2004·Toxicology Mechanisms and Methods·Supratim Choudhuri
Apr 17, 2010·Trends in Genetics : TIG·Sanaz Farajollahi, Stefan Maas
Oct 22, 2008·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·S D BuckinghamD B Sattelle
Jun 27, 2006·Journal of Cellular and Molecular Medicine·Rachel Aronoff, C C H Petersen
Oct 14, 2009·The Journal of Comparative Neurology·Erik J RagsdaleJames G Baldwin
Dec 1, 2011·International Journal for Parasitology. Drugs and Drug Resistance·Adrian J Wolstenholme
Sep 30, 2016·International Journal for Parasitology. Drugs and Drug Resistance·Thangadurai ManiRoger K Prichard

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