Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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 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.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Genetic screen for mutations suppressing the hyper-reversal phenotype of lurcher worms.
Figure 2: sol-1(ak63) phenocopies glr-1(ky176).
Figure 3: sol-1(ak63) does not affect GLR-1 expression, localization or membrane insertion.
Figure 4: Non-NMDA-gated currents are eliminated in both glr-1(ky176) and sol-1(ak63) mutants.
Figure 5: SOL-1 is a predicted type I transmembrane protein that interacts with GLR-1.


  1. Zuo, J. et al. Neurodegeneration in Lurcher mice caused by mutation in δ2 glutamate receptor gene. Nature 388, 769–773 (1997)

    ADS  CAS  Article  PubMed  Google Scholar 

  2. Bork, P. & Beckmann, G. The CUB domain. A widespread module in developmentally regulated proteins. J. Mol. Biol. 231, 539–545 (1993)

    CAS  Article  PubMed  Google Scholar 

  3. Varela, P. F. et al. The 2.4 Å resolution crystal structure of boar seminal plasma PSP-I/PSP-II: a zona pellucida-binding glycoprotein heterodimer of the spermadhesin family built by a CUB domain architecture. J. Mol. Biol. 274, 635–649 (1997)

    CAS  Article  PubMed  Google Scholar 

  4. Dingledine, R., Borges, K., Bowie, D. & Traynelis, S. F. The glutamate receptor ion channels. Pharmacol. Rev. 51, 7–61 (1999)

    CAS  PubMed  Google Scholar 

  5. Sheng, M. & Kim, M. J. Postsynaptic signaling and plasticity mechanisms. Science 298, 776–780 (2002)

    ADS  CAS  Article  PubMed  Google Scholar 

  6. Kohda, K., Wang, Y. & Yuzaki, M. Mutation of a glutamate receptor motif reveals its role in gating and δ2 receptor channel properties. Nature Neurosci. 3, 315–322 (2000)

    CAS  Article  PubMed  Google Scholar 

  7. Maricq, A. V., Peckol, E., Driscoll, M. & Bargmann, C. I. Mechanosensory signalling in C. elegans mediated by the GLR-1 glutamate receptor. Nature 378, 78–81 (1995)

    ADS  CAS  Article  PubMed  Google Scholar 

  8. Hart, A. C., Sims, S. & Kaplan, J. M. Synaptic code for sensory modalities revealed by C. elegans GLR-1 glutamate receptor. Nature 378, 82–85 (1995)

    ADS  CAS  Article  PubMed  Google Scholar 

  9. Zheng, Y., Brockie, P. J., Mellem, J. E., Madsen, D. M. & Maricq, A. V. Neuronal control of locomotion in C. elegans is modified by a dominant mutation in the GLR-1 ionotropic glutamate receptor. Neuron 24, 347–361 (1999)

    CAS  Article  PubMed  Google Scholar 

  10. Stein, L., Sternberg, P., Durbin, R., Thierry-Mieg, J. & Spieth, J. WormBase: network access to the genome and biology of Caenorhabditis elegans. Nucleic Acids Res. 29, 82–86 (2001)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. Gregory, L. A., Thielens, N. M., Arlaud, G. J. & Fontecilla-Camps, J. C. Gaboriaud C. X-ray structure of the Ca2+-binding interaction domain of C1s: insights into the assembly of the C1 complex of complement. J. Biol. Chem. 278, 32157–32164 (2003)

    CAS  Article  PubMed  Google Scholar 

  12. Mellem, J. E., Brockie, P. J., Zheng, Y., Madsen, D. M. & Maricq, A. V. Decoding of polymodal sensory stimuli by postsynaptic glutamate receptors in C. elegans. Neuron 36, 933–944 (2002)

    CAS  Article  PubMed  Google Scholar 

  13. Hilliard, M. A., Bargmann, C. I. & Bazzicalupo, P. C. elegans responds to chemical repellents by integrating sensory inputs from the head and the tail. Curr. Biol. 12, 730–734 (2002)

    CAS  Article  PubMed  Google Scholar 

  14. Rongo, C., Whitfield, C. W., Rodal, A., Kim, S. K. & Kaplan, J. M. LIN-10 is a shared component of the polarized protein localization pathways in neurons and epithelia. Cell 94, 751–759 (1998)

    CAS  Article  PubMed  Google Scholar 

  15. Christensen, M. et al. A primary culture system for functional analysis of C. elegans neurons and muscle cells. Neuron 33, 503–514 (2002)

    CAS  Article  PubMed  Google Scholar 

  16. Brockie, P. J., Mellem, J. E., Hills, T., Madsen, D. M. & Maricq, A. V. The C. elegans glutamate receptor subunit NMR-1 is required for slow NMDA-activated currents that regulate reversal frequency during locomotion. Neuron 31, 617–630 (2001)

    CAS  Article  PubMed  Google Scholar 

  17. Brockie, P. J., Madsen, D. M., Zheng, Y., Mellem, J. & Maricq, A. V. Differential expression of glutamate receptor subunits in the nervous system of Caenorhabditis elegans and their regulation by the homeodomain protein UNC-42. J. Neurosci. 21, 1510–1522 (2001)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. Chelur, D. S. et al. The mechanosensory protein MEC-6 is a subunit of the C. elegans touch-cell degenerin channel. Nature 420, 669–673 (2002)

    ADS  CAS  Article  PubMed  Google Scholar 

  19. Michishita, M. et al. A novel gene, Btcl1, encoding CUB and LDLa domains is expressed in restricted areas of mouse brain. Biochem. Biophys. Res. Commun. 306, 680–686 (2003)

    CAS  Article  PubMed  Google Scholar 

  20. Stohr, H., Berger, C., Frohlich, S. & Weber, B. H. A novel gene encoding a putative transmembrane protein with two extracellular CUB domains and a low-density lipoprotein class A module: isolation of alternatively spliced isoforms in retina and brain. Gene 286, 223–231 (2002)

    CAS  Article  PubMed  Google Scholar 

  21. He, Z. & Tessier-Lavigne, M. Neuropilin is a receptor for the axonal chemorepellent Semaphorin III. Cell 90, 739–751 (1997)

    CAS  Article  PubMed  Google Scholar 

  22. Kolodkin, A. L. et al. Neuropilin is a semaphorin III receptor. Cell 90, 753–762 (1997)

    CAS  Article  PubMed  Google Scholar 

  23. Altschul, S. F. et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389–3402 (1997)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. Armstrong, N., Sun, Y., Chen, G. Q. & Gouaux, E. Structure of a glutamate-receptor ligand-binding core in complex with kainate. Nature 395, 913–917 (1998)

    ADS  CAS  Article  PubMed  Google Scholar 

  25. Shi, S., Hayashi, Y., Esteban, J. A. & Malinow, R. Subunit-specific rules governing AMPA receptor trafficking to synapses in hippocampal pyramidal neurons. Cell 105, 331–343 (2001)

    CAS  Article  PubMed  Google Scholar 

  26. Anderson, P. in Methods in Cell Biology (eds Epstein, H. F. & Shakes, D. C.) 31–58 (Academic, New York, 1995)

    Google Scholar 

  27. Wilson, R. et al. 2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans. Nature 368, 32–38 (1994)

    ADS  CAS  Article  PubMed  Google Scholar 

  28. Gasteiger, E. et al. ExPASy: The proteomics server for in-depth protein knowledge and analysis. Nucleic Acids Res. 31, 3784–3788 (2003)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

Download references


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.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Andres V. Maricq.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Figure 1: sol-1 genomic location and organization (JPG 29 kb)


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)


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)

Supplementary Figure Legends. (DOC 21 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing