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, dreammist ( dmist ), whose loss results in 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. Since atpa1a3a and dmist 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. Significance statement Sleep is an essential behavioral state, but the genes that regulate sleep and wake states are still being uncovered. A viral insertion screen in zebrafish identified a novel sleep mutant called dreammist , in which a small, highly-conserved transmembrane protein is disrupted. The discovery of dreammist highlights the importance of a class of small transmembrane-protein modulators of the sodium pump in setting appropriate sleep duration.

The zebrafish mutantdreammistimplicates sodium homeostasis in sleep regulation