title: SOL-1 is a CUB-domain protein required for GLR-1 glutamate receptor function in C. elegans.
abstract: Ionotropic glutamate receptors (iGluRs) mediate most excitatory synaptic signalling between neurons. Binding of the neurotransmitter glutamate causes a conformational change in these receptors that gates open a transmembrane pore through which ions can pass. The gating of iGluRs is crucially dependent on a conserved amino acid that was first identified in the 'lurcher' ataxic mouse. Through a screen for modifiers of iGluR function in a transgenic strain of Caenorhabditis elegans expressing a GLR-1 subunit containing the lurcher mutation, we identify suppressor of lurcher (sol-1). This gene encodes a transmembrane protein that is predicted to contain four extracellular beta-barrel-forming domains known as CUB domains. SOL-1 and GLR-1 are colocalized at the cell surface and can be co-immunoprecipitated. By recording from neurons expressing GLR-1, we show that SOL-1 is an accessory protein that is selectively required for glutamate-gated currents. We propose that SOL-1 participates in the gating of non-NMDA (N-methyl-D-aspartate) iGluRs, thereby providing a previously unknown mechanism of regulation for this important class of neurotransmitter receptor.
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, Utah 84112-0840, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Jerry E
authors.initials: JE
authors.lastname: Mellem
authors.forename: Penelope J
authors.initials: PJ
authors.lastname: Brockie
authors.forename: David M
authors.initials: DM
authors.lastname: Madsen
authors.forename: Andres V
authors.initials: AV
authors.lastname: Maricq
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004553:Electric Conductivity; D018698:Glutamic Acid / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D017434:Protein Structure, Tertiary; D018091:Receptors, AMPA; D017470:Receptors, Glutamate / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; C481340:SOL-1 protein, C elegans; C096470:glr-1 protein, C elegans; D018698:Glutamic Acid