Beschreibung:
<jats:p>Sleep is a nearly universal feature of animal behaviour, yet many of the molecular, genetic, and neuronal substrates that orchestrate sleep/wake transitions lie undiscovered. Employing a viral insertion sleep screen in larval zebrafish, we identified a novel gene, <jats:italic>dreammist</jats:italic> (<jats:italic>dmist</jats:italic>), whose loss results in behavioural hyperactivity and reduced sleep at night. The neuronally expressed <jats:italic>dmist</jats:italic> gene is conserved across vertebrates and encodes a small single-pass transmembrane protein that is structurally similar to the Na<jats:sup>+</jats:sup>,K<jats:sup>+</jats:sup>-ATPase regulator, FXYD1/Phospholemman. Disruption of either <jats:italic>fxyd1</jats:italic> or <jats:italic>atp1a3a</jats:italic>, a Na<jats:sup>+</jats:sup>,K<jats:sup>+</jats:sup>-ATPase alpha-3 subunit associated with several heritable movement disorders in humans, led to decreased night-time sleep. Since <jats:italic>atpa1a3a</jats:italic> and <jats:italic>dmist</jats:italic> mutants have elevated intracellular Na<jats:sup>+</jats:sup> levels and non-additive effects on sleep amount at night, we propose that Dmist-dependent enhancement of Na<jats:sup>+</jats:sup> pump function modulates neuronal excitability to maintain normal sleep behaviour.</jats:p>