A genetic screen identifies dreammist as regulator of sleep

Authors : 

Ida L. Barlow1,2 , Eirinn Mackay1,3 , Emily Wheater1,4 , Aimee Goel1 , Sumi Lim1 2 , Steve Zimmerman5 , Ian Woods6 , David A. Prober7 , and Jason Rihel1,*

ABSTRACT 25 Sleep is a nearly universal feature of animal behaviour, yet many of the molecular, genetic, 26 and neuronal substrates that orchestrate sleep/wake transitions lie undiscovered. Employing a 27 viral insertion sleep screen in larval zebrafish, we identified a novel mutant, dreammist (dmist), 28 with altered sleep-wake dynamics. CRISPR/Cas9-mediated disruption of dmist also led to 29 behavioural hyperactivity and reduced sleep at night. The neuronally expressed dmist gene is 30 conserved across vertebrates and encodes a small single-pass transmembrane protein that is structurally similar to the Na+ ,K+ 31 -ATPase regulator, FXYD1/Phospholemman. Disruption of either fxyd1 or atp1a3a, a Na+ ,K+ 32 -ATPase alpha-3 subunit associated with several heritable movement disorders in humans, led to decreased night-time sleep. As intracellular Na+ 33 34 concentration is disrupted in dmist mutant brains after high neuronal activity similarly to 35 atp1a3a mutants, but is also elevated specifically at night, we propose that sleep-wake stability is modulated by Dmist-dependent changes to Na+ 36 pump function during sleep homeostatic 37 challenge and at specific times of the day-night cycle


Link to publication : https://www.biorxiv.org/content/10.1101/2020.11.18.388736v1