The zebrafish mutant <i>dreammist</i> implicates sodium homeostasis in sleep regulation.

Abstract

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, <i>dreammist</i> (<i>dmist</i>), whose loss results in behavioural hyperactivity and reduced sleep at night. The neuronally expressed <i>dmist</i> gene is conserved across vertebrates and encodes a small single-pass transmembrane protein that is structurally similar to the Na⁺,K⁺-ATPase regulator, FXYD1/Phospholemman. Disruption of either <i>fxyd1</i> or <i>atp1a3a</i>, a Na⁺,K⁺-ATPase alpha-3 subunit associated with several heritable movement disorders in humans, led to decreased night-time sleep. Since <i>atpa1a3a</i> and <i>dmist</i> mutants have elevated intracellular Na⁺ levels and non-additive effects on sleep amount at night, we propose that Dmist-dependent enhancement of Na⁺ pump function modulates neuronal excitability to maintain normal sleep behaviour.