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A glial amino-acid transporter controls synapse strength and courtship in Drosophila

Nature Neuroscience volume 11, pages 54–61 (2008)Cite this article

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Abstract

Mate choice is an evolutionarily critical decision that requires the detection of multiple sex-specific signals followed by central integration of these signals to direct appropriate behavior. The mechanisms controlling mate choice remain poorly understood. Here, we show that the glial amino-acid transporter genderblind controls whether Drosophila melanogaster males will attempt to mate with other males. Genderblind (gb) mutant males showed no alteration in heterosexual courtship or copulation, but were attracted to normally unappealing male species-specific chemosensory cues. As a result, genderblind mutant males courted and attempted to copulate with other Drosophila males. This homosexual behavior could be induced within hours using inducible RNAi, suggesting that genderblind controls nervous system function rather than its development. Consistent with this, and indicating that glial genderblind regulates ambient extracellular glutamate to suppress glutamatergic synapse strength in vivo, homosexual behavior could be turned on and off by altering glutamatergic transmission pharmacologically and/or genetically.

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Figure 1: gb mutant males are 'genderblind'.
Figure 2: gb mutant males show altered responses to species-specific chemical sexual cues.
Figure 3: Genderblind (genderblind) protein is expressed in central glia surrounding glutamatergic neurons.
Figure 4: Drosophila male homosexual courtship is controlled by the strength of glutamatergic neurotransmission.

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Change history

  • 16 December 2007

    In the version of this article originally published online, the title was incorrect. The correct title is "A glial amino-acid transporter controls synapse strength and courtship in Drosophila." This error has been corrected for all versions of the article.

  • 11 January 2008

    In the version of this article originally published online, the titles and captions of supplementary videos were missing. The error has been corrected online.

References

  1. Spieth, H.T. Courtship behavior in Drosophila. Annu. Rev. Entomol. 19, 385–405 (1974).

    Article  CAS  Google Scholar 

  2. Greenspan, R.J. & Ferveur, J.F. Courtship in Drosophila. Annu. Rev. Genet. 34, 205–232 (2000).

    Article  CAS  Google Scholar 

  3. Billeter, J.C., Rideout, E.J., Dornan, A.J. & Goodwin, S.F. Control of male sexual behavior in Drosophila by the sex determination pathway. Curr. Biol. 16, R766–R776 (2006).

    Article  CAS  Google Scholar 

  4. Shirangi, T.R. & McKeown, M. Sex in flies: what 'body-mind' dichotomy? Dev. Biol. 306, 10–19 (2007).

    Article  CAS  Google Scholar 

  5. van der Goes van Naters, W. & Carlson, J.R. Receptors and neurons for fly odors in Drosophila. Curr. Biol. 17, 606–612 (2007).

    Article  CAS  Google Scholar 

  6. Lacaille, F. et al. An inhibitory sex pheromone tastes bitter for Drosophila males. PLoS ONE 2, e661 (2007).

    Article  Google Scholar 

  7. Marcillac, F., Grosjean, Y. & Ferveur, J.F. A single mutation alters production and discrimination of Drosophila sex pheromones. Proc. Biol. Sci. 272, 303–309 (2005).

    Article  CAS  Google Scholar 

  8. Ejima, A. et al. Generalization of courtship learning in Drosophila is mediated by cis-vaccenyl acetate. Curr. Biol. 17, 599–605 (2007).

    Article  CAS  Google Scholar 

  9. Augustin, H., Grosjean, Y., Chen, K., Sheng, Q. & Featherstone, D.E. Nonvesicular release of glutamate by glial xCT transporters suppresses glutamate receptor clustering in vivo. J. Neurosci. 27, 111–123 (2007).

    Article  CAS  Google Scholar 

  10. Featherstone, D.E. & Shippy, S.A. Regulation of synaptic transmission by ambient extracellular glutamate. Neuroscientist. published online 18 October 2007 (doi:10.1177/1073858407308518).

  11. Kurtovic, A., Widmer, A. & Dickson, B.J. A single class of olfactory neurons mediates behavioural responses to a Drosophila sex pheromone. Nature 446, 542–546 (2007).

    Article  CAS  Google Scholar 

  12. Jefferis, G.S. et al. Comprehensive maps of Drosophila higher olfactory centers: spatially segregated fruit and pheromone representation. Cell 128, 1187–1203 (2007).

    Article  CAS  Google Scholar 

  13. Winther, A.M., Acebes, A. & Ferrus, A. Tachykinin-related peptides modulate odor perception and locomotor activity in Drosophila. Mol. Cell. Neurosci. 31, 399–406 (2006).

    Article  CAS  Google Scholar 

  14. Rajewsky, N. MicroRNA target predictions in animals. Nat. Genet. 38 Suppl, S8–S13 (2006).

    Article  CAS  Google Scholar 

  15. Dietzl, G. et al. A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila. Nature 448, 151–156 (2007).

    Article  CAS  Google Scholar 

  16. Daniels, R.W. et al. Increased expression of the Drosophila vesicular glutamate transporter leads to excess glutamate release and a compensatory decrease in quantal content. J. Neurosci. 24, 10466–10474 (2004).

    Article  CAS  Google Scholar 

  17. Bogdanik, L. et al. The Drosophila metabotropic glutamate receptor DmGluRA regulates activity-dependent synaptic facilitation and fine synaptic morphology. J. Neurosci. 24, 9105–9116 (2004).

    Article  CAS  Google Scholar 

  18. Zhang, S.D. & Odenwald, W.F. Misexpression of the white (w) gene triggers male-male courtship in Drosophila. Proc. Natl. Acad. Sci. USA 92, 5525–5529 (1995).

    Article  CAS  Google Scholar 

  19. Hing, A.L. & Carlson, J.R. Male-male courtship behavior induced by ectopic expression of the Drosophila white gene: role of sensory function and age. J. Neurobiol. 30, 454–464 (1996).

    Article  CAS  Google Scholar 

  20. An, X., Armstrong, J.D., Kaiser, K. & O'Dell, K.M. The effects of ectopic white and transformer expression on Drosophila courtship behavior. J. Neurogenet. 14, 227–243, 271 (2000).

    Article  CAS  Google Scholar 

  21. Svetec, N., Houot, B. & Ferveur, J.F. Effect of genes, social experience, and their interaction on the courtship behaviour of transgenic Drosophila males. Genet. Res. 85, 183–193 (2005).

    Article  CAS  Google Scholar 

  22. Mahr, A. & Aberle, H. The expression pattern of the Drosophila vesicular glutamate transporter: a marker protein for motoneurons and glutamatergic centers in the brain. Gene Expr. Patterns 6, 299–309 (2006).

    Article  CAS  Google Scholar 

  23. Schuster, C.M., Ultsch, A., Schmitt, B. & Betz, H. Molecular analysis of Drosophila glutamate receptors. EXS 63, 234–240 (1993).

    CAS  PubMed  Google Scholar 

  24. Tomancak, P. et al. Systematic determination of patterns of gene expression during Drosophila embryogenesis. Genome Biol. [online] 3, RESEARCH0088 (2002) (doi:10.1186/gb-2002-3-12-research0088).

  25. Featherstone, D.E. et al. An essential Drosophila glutamate receptor subunit that functions in both central neuropil and neuromuscular junction. J. Neurosci. 25, 3199–3208 (2005).

    Article  CAS  Google Scholar 

  26. Xia, S. et al. NMDA receptors mediate olfactory learning and memory in Drosophila. Curr. Biol. 15, 603–615 (2005).

    Article  CAS  Google Scholar 

  27. Sato, H., Tamba, M., Ishii, T. & Bannai, S. Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins. J. Biol. Chem. 274, 11455–11458 (1999).

    Article  CAS  Google Scholar 

  28. Baker, D.A., Xi, Z.X., Shen, H., Swanson, C.J. & Kalivas, P.W. The origin and neuronal function of in vivo nonsynaptic glutamate. J. Neurosci. 22, 9134–9141 (2002).

    Article  CAS  Google Scholar 

  29. Piyankarage, S.C., Augustin, H., Featherstone, D.E. & Shippy, S.A. Amino acid analysis of hemolymph from individual Drosophila melanogaster. Anal. Chem. (in the press) (2008).

  30. Juhasz, G. et al. Sleep promoting effect of a putative glial gamma-aminobutyric acid uptake blocker applied in the thalamus of cats. Eur. J. Pharmacol. 209, 131–133 (1991).

    Article  CAS  Google Scholar 

  31. Lena, I. et al. Variations in extracellular levels of dopamine, noradrenaline, glutamate and aspartate across the sleep-wake cycle in the medial prefrontal cortex and nucleus accumbens of freely moving rats. J. Neurosci. Res. 81, 891–899 (2005).

    Article  CAS  Google Scholar 

  32. Castaneda, T.R., de Prado, B.M., Prieto, D. & Mora, F. Circadian rhythms of dopamine, glutamate and GABA in the striatum and nucleus accumbens of the awake rat: modulation by light. J. Pineal Res. 36, 177–185 (2004).

    Article  CAS  Google Scholar 

  33. Lee, Y., Gaskins, D., Anand, A. & Shekhar, A. Glia mechanisms in mood regulation: a novel model of mood disorders. Psychopharmacology (Berl.) 191, 55–65 (2007).

    Article  Google Scholar 

  34. Adachi, A., Natesan, A.K., Whitfield-Rucker, M.G., Weigum, S.E. & Cassone, V.M. Functional melatonin receptors and metabolic coupling in cultured chick astrocytes. Glia 39, 268–278 (2002).

    Article  Google Scholar 

  35. Baker, D.A. et al. Contribution of cystine-glutamate antiporters to the psychotomimetic effects of phencyclidine. Neuropsychopharmacology. advance online publication 29 August 2007 (doi:10.1038/sj.npp.1301532).

  36. Baker, D.A. et al. Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse. Nat. Neurosci. 6, 743–749 (2003).

    Article  CAS  Google Scholar 

  37. Lim, J., Lam, Y.C., Kistler, J. & Donaldson, P.J. Molecular characterization of the cystine/glutamate exchanger and the excitatory amino acid transporters in the rat lens. Invest. Ophthalmol. Vis. Sci. 46, 2869–2877 (2005).

    Article  Google Scholar 

  38. Burdo, J., Dargusch, R. & Schubert, D. Distribution of the cystine/glutamate antiporter system xc– in the brain, kidney and duodenum. J. Histochem. Cytochem. 54, 549–557 (2006).

    Article  CAS  Google Scholar 

  39. Shih, A.Y. et al. Cystine/glutamate exchange modulates glutathione supply for neuroprotection from oxidative stress and cell proliferation. J. Neurosci. 26, 10514–10523 (2006).

    Article  CAS  Google Scholar 

  40. Kimchi, T., Xu, J. & Dulac, C. A functional circuit underlying male sexual behaviour in the female mouse brain. Nature 448, 1009–1014 (2007).

    Article  CAS  Google Scholar 

  41. Marcillac, F., Bousquet, F., Alabouvette, J., Savarit, F. & Ferveur, J.F. A mutation with major effects on Drosophila melanogaster sex pheromones. Genetics 171, 1617–1628 (2005).

    Article  CAS  Google Scholar 

  42. Balakireva, M., Stocker, R.F., Gendre, N. & Ferveur, J.F. Voila, a new Drosophila courtship variant that affects the nervous system: behavioral, neural and genetic characterization. J. Neurosci. 18, 4335–4343 (1998).

    Article  CAS  Google Scholar 

  43. Grosjean, Y., Balakireva, M., Dartevelle, L. & Ferveur, J.F. PGal4 excision reveals the pleiotropic effects of Voila, a Drosophila locus that affects development and courtship behaviour. Genet. Res. 77, 239–250 (2001).

    Article  CAS  Google Scholar 

  44. Woodard, C., Huang, T., Sun, H., Helfand, S.L. & Carlson, J. Genetic analysis of olfactory behavior in Drosophila: a new screen yields the ota mutants. Genetics 123, 315–326 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Roberts, D.B. Drosophila: A Practical Approach 2nd edn (Oxford University Press, Oxford, 1998).

  46. Horz, H.-P., Kurtz, R., Batey, D. & Bohannan, B. Monitoring microbial populations using real-time qPCR on the MJ research Opticon 2 system. MJ Research Application Note 3, 1–4 (2004).

    Google Scholar 

  47. Bellen, H.J. et al. The BDGP gene disruption project: single transposon insertions associated with 40% of Drosophila genes. Genetics 167, 761–781 (2004).

    Article  CAS  Google Scholar 

  48. Zars, T., Fischer, M., Schulz, R. & Heisenberg, M. Localization of a short-term memory in Drosophila. Science 288, 672–675 (2000).

    Article  CAS  Google Scholar 

  49. Masuda-Nakagawa, L.M., Tanaka, N.K. & O'Kane, C.J. Stereotypic and random patterns of connectivity in the larval mushroom body calyx of Drosophila. Proc. Natl. Acad. Sci. USA 102, 19027–19032 (2005).

    Article  CAS  Google Scholar 

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Acknowledgements

We would like to thank P.-S. Ng for technical assistance, A. DiAntonio, T. Zars, R.F. Stocker, K. Broadie and H. for transgenic fly lines, W. Francke (University of Hamburg) for the synthesis of the 7-tricosene chemical, and B. Taylor (Oregon State) for helpful discussion and ideas. Other essential reagents were provided by the Drosophila Gene Disruption Project, the Vienna Drosophila RNAi Center and the Bloomington and Tucson Drosophila Stock Centers. Funding for this work was provided by grants from the Muscular Dystrophy Association and US National Institute of Neurological Disorders and Stroke (R01NS045628) to D.E.F., and by the Centre National de la Recherche Scientifique to J.-F.F.

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Author notes

  1. Yael Grosjean

    Present address: Present address: Center of Integrative Genomics, Genopode Building, Room 3033, University of Lausanne, CH-1015 Lausanne, Switzerland.,

Authors and Affiliations

  1. Biological Sciences, University of Illinois at Chicago, 840 W Taylor Street (MC 067), Chicago, Illinois, USA

    Yael Grosjean, Hrvoje Augustin & David E Featherstone

  2. Université de Bourgogne, UMR-5548 Centre National de la Recherche Scientifique 5548, 6 Boulevard Gabriel, Dijon, 21000, France

    Micheline Grillet & Jean-François Ferveur

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Contributions

Y.G. made the original observation that gb mutant males courted each other and was responsible for all genetic and pharmacological manipulations, immunohistochemistry and most of the behavioral experiments and analysis. M.G. was responsible for some locomotory tests, the heterosexual copulation measurements and the desat mutant male experiments and contributed to decapitated partner courtship tests. H.A. was responsible for the gb real-time RT-PCR and GB immunoblot data. D.E.F, Y.G. and J-F.F. were responsible for experimental design and interpretation of results and writing the article.

Corresponding author

Correspondence to David E Featherstone.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–4 (PDF 1956 kb)

Supplementary Video 1

This video shows six wild-type (Oregon R) males. They display little courtship behavior. (WMV 3057 kb)

Supplementary Video 2

This video shows six gb[KG07905] mutant males. They display frequent and extensive homosexual courtship behavior. (WMV 3047 kb)

Supplementary Video 3

This video shows six precise excision males (flies where the gb[KG07095] transposon has been precisely excised). They display very little courtship behavior. (WMV 3056 kb)

Supplementary Video 4

This video shows six males of the genotype TubGal4/UAS-DVGluT. In these flies, the Drosophila vesicular glutamate transporter DVGluT has been overexpressed to increase glutamatergic synapse strength. These flies display frequent and extensive homosexual courtship behavior. (WMV 1825 kb)

Supplementary Video 5

This video shows six gb[KG07095] mutant males that have drunk apple juice containing gamma-D-glutamylglycine (gamma-DGG), a competitive glutamate receptor antagonist that weakens glutamatergic synapse strength. These display very little courtship behavior. (WMV 244 kb)

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Grosjean, Y., Grillet, M., Augustin, H. et al. A glial amino-acid transporter controls synapse strength and courtship in Drosophila. Nat Neurosci 11, 54–61 (2008). https://doi.org/10.1038/nn2019

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