A genetic screen identifies dreammist as a regulator of sleep

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 mutant, dreammist (dmist), with altered sleep-wake dynamics. CRISPR/Cas9-mediated disruption of dmist also led to behavioural hyperactivity and reduced sleep at night. The neuronally expressed dmist 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 fxyd1 or atp1a3a, a Na+,K+-ATPase alpha-3 subunit associated with several heritable movement disorders in humans, led to decreased night-time sleep. As intracellular Na+ concentration is disrupted in dmist mutant brains after high neuronal activity similarly to atp1a3a mutants, but is also elevated specifically at night, we propose that sleep-wake stability is modulated by Dmist-dependent changes to Na+ pump function during sleep homeostatic challenge and at specific times of the day-night cycle.