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bioRxiv · 10.1101/2020.11.18.388736

A genetic screen identifies dreammist as a regulator of sleep

Barlow, I. L.·Mackay, E.·Wheater, E.·Goel, A.·Lim, S.·Zimmerman, S.·Woods, I.·Prober, D. A.·Rihel, J.
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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 statementSleep 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.

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Barlow, I. L., Mackay, E., Wheater, E., Goel, A., Lim, S., Zimmerman, S., Woods, I., Prober, D. A., Rihel, J.. 2020-11-18. A genetic screen identifies dreammist as a regulator of sleep. https://doi.org/10.1101/2020.11.18.388736

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