Barlow, Ida L;
Mackay, Eirinn;
Wheater, Emily;
Goel, Aimee;
Lim, Sumi;
Zimmerman, Steve;
Woods, Ian;
... Rihel, Jason; + view all
(2023)
The zebrafish mutant dreammist implicates sodium homeostasis in sleep regulation.
eLife
, 12
, Article RP87521. 10.7554/elife.87521.3.
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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.
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