Differential expression of glutamate receptor subunits in the nervous system of Caenorhabditis elegans and their regulation by the homeodomain protein UNC-42.
In almost all nervous systems, rapid excitatory synaptic communication is mediated by a diversity of ionotropic glutamate receptors. In Caenorhabditis elegans, 10 putative ionotropic glutamate receptor subunits have been identified, a surprising number for an organism with only 302 neurons. Sequence analysis of the predicted proteins identified two NMDA and eight non-NMDA receptor subunits. Here we describe the complete distribution of these subunits in the nervous system of C. elegans. Receptor subunits were found almost exclusively in interneurons and motor neurons, but no expression was detected in muscle cells. Interestingly, some neurons expressed only a single subunit, suggesting that these may form functional homomeric channels. Conversely, interneurons of the locomotory control circuit (AVA, AVB, AVD, AVE, and PVC) coexpressed up to six subunits, suggesting that these subunits interact to generate a diversity of heteromeric glutamate receptor channels that regulate various aspects of worm movement. We also show that expression of these subunits in this circuit is differentially regulated by the homeodomain protein UNC-42 and that UNC-42 is also required for axonal pathfinding of neurons in the circuit. In wild-type worms, the axons of AVA, AVD, and AVE lie in the ventral cord, whereas in unc-42 mutants, the axons are anteriorly, laterally, or dorsally displaced, and the mutant worms have sensory and locomotory defects.
Department of Biology, University of Utah, Salt Lake City, Utah 84112-0840, USA.
P J
PJ
Brockie
D M
DM
Madsen
Y
Y
Zheng
J
J
Mellem
A V
AV
Maricq
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism; D001522:Behavior, Animal; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D049452:Green Fluorescent Proteins; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009069:Movement Disorders / Q000235:genetics; D009132:Muscles / Q000166:cytology / Q000378:metabolism; D009154:Mutation; D009420:Nervous System / Q000378:metabolism*; D010641:Phenotype; D010802:Phylogeny; D021122:Protein Subunits; D018091:Receptors, AMPA; D017470:Receptors, Glutamate / Q000096:biosynthesis* / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012678:Sensation Disorders / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D018398:Homeodomain Proteins; D008164:Luminescent Proteins; D021122:Protein Subunits; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins; C096470:glr-1 protein, C elegans; C119682:unc-42 protein, C elegans; D049452:Green Fluorescent Proteins