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A neuron–glia interaction involving GABA transaminase contributes to sleep loss in sleepless mutants

Molecular Psychiatry volume 20, pages 240–251 (2015)Cite this article

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Abstract

Sleep is an essential process and yet mechanisms underlying it are not well understood. Loss of the Drosophila quiver/sleepless (qvr/sss) gene increases neuronal excitability and diminishes daily sleep, providing an excellent model for exploring the underpinnings of sleep regulation. Here, we used a proteomic approach to identify proteins altered in sss brains. We report that loss of sleepless post-transcriptionally elevates the CG7433 protein, a mitochondrial γ-aminobutyric acid transaminase (GABAT), and reduces GABA in fly brains. Loss of GABAT increases daily sleep and improves sleep consolidation, indicating that GABAT promotes wakefulness. Importantly, disruption of the GABAT gene completely suppresses the sleep phenotype of sss mutants, demonstrating that GABAT is required for loss of sleep in sss mutants. While SSS acts in distinct populations of neurons, GABAT acts in glia to reduce sleep in sss flies. Our results identify a novel mechanism of interaction between neurons and glia that is important for the regulation of sleep.

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Acknowledgements

We thank the Penn Proteomics Core for conducting the 2D-DIGE gel analysis, Erin Forbeck and Xiaobo Wan for help with the HPLC analysis and members of the laboratory for helpful discussions.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, Chevy Chase, MD, USA,

    W-F Chen, M Sowcik & A Sehgal

  2. Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA, USA,

    W-F Chen, S Maguire, W Luo & A Sehgal

  3. Thomas Jefferson University, Philadelphia, PA, USA

    K Koh

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  1. W-F Chen
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Correspondence to A Sehgal.

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Chen, WF., Maguire, S., Sowcik, M. et al. A neuron–glia interaction involving GABA transaminase contributes to sleep loss in sleepless mutants. Mol Psychiatry 20, 240–251 (2015). https://doi.org/10.1038/mp.2014.11

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