SOL-1 is a CUB-domain protein required for GLR-1 glutamate receptor function in C. elegans.
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.
Zheng
Yi
Y
Department of Biology, University of Utah, Salt Lake City, Utah 84112-0840, USA.
Mellem
Jerry E
JE
Brockie
Penelope J
PJ
Madsen
David M
DM
Maricq
Andres V
AV
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*
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