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 mouse1. 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 β-barrel-forming domains known as CUB domains2,3. 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.
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Acknowledgements
We thank M. Vetter and members of the Maricq laboratory for comments on the manuscript; L. Jack for generating transgenic strains; C. Walker, N. Strutz, M. Francis and A. Ebens for discussions; C. Rongo and J. Kaplan for the nuIs25 strain; and A. Gottschalk and W. Schafer for help with immunolabelling live worms. Some strains were provided by the Caenorhabditis Genetics Center. This research was supported by the Burroughs Wellcome Foundation, and by a grant from the NIH.
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Supplementary information
41586_2004_BFnature02244_MOESM2_ESM.jpg
Supplementary Figure 2: Sequence alignment of CUB domains from various CUB domain proteins (modified from 11) and the 4 predicted CUB domains of SOL-1. (JPG 79 kb)
41586_2004_BFnature02244_MOESM3_ESM.jpg
Supplementary Figure 3: Confocal images of GFP (top), anti-GFP antibody staining (middle) and the merged images (bottom) in transgenic sol-1(ak63) worms that expressed GFP::GLR-2 (extracellular GFP) injected with Alexa 594 conjugated rabbit anti-GFP polyclonal sera. (JPG 91 kb)
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Zheng, Y., Mellem, J., Brockie, P. et al. SOL-1 is a CUB-domain protein required for GLR-1 glutamate receptor function in C. elegans. Nature 427, 451–457 (2004). https://doi.org/10.1038/nature02244
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DOI: https://doi.org/10.1038/nature02244
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