SOL-1 is a CUB-domain protein required for GLR-1 glutamate receptor function in C. elegans

Nature. 2004 Jan 29;427(6973):451-7. doi: 10.1038/nature02244.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biological Transport
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / chemistry*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cells, Cultured
  • Electric Conductivity
  • Glutamic Acid / metabolism
  • Molecular Sequence Data
  • Neurons / metabolism
  • Protein Structure, Tertiary
  • Receptors, AMPA
  • Receptors, Glutamate / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Receptors, AMPA
  • Receptors, Glutamate
  • SOL-1 protein, C elegans
  • glr-1 protein, C elegans
  • Glutamic Acid