title: A neuron-glia interaction involving GABA transaminase contributes to sleep loss in sleepless mutants.
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.
authors.affiliation: 1] Howard Hughes Medical Institute, Chevy Chase, MD, USA [2] Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: W-F
authors.initials: WF
authors.lastname: Chen
authors.affiliation: Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Maguire
authors.affiliation: Howard Hughes Medical Institute, Chevy Chase, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Sowcik
authors.affiliation: Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Luo
authors.affiliation: Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Koh
authors.affiliation: 1] Howard Hughes Medical Institute, Chevy Chase, MD, USA [2] Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sehgal
mesh_terms: D000612:4-Aminobutyrate Transaminase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics*; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; C530371:Qvr protein, Drosophila; D000612:4-Aminobutyrate Transaminase