The zebrafish mutant dreammist implicates sodium homeostasis in sleep regulation

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 resul...

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Main Authors: Ida L Barlow, Eirinn Mackay, Emily Wheater, Aimee Goel, Sumi Lim, Steve Zimmerman, Ian Woods, David A Prober, Jason Rihel
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2023-08-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/87521
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author Ida L Barlow
Eirinn Mackay
Emily Wheater
Aimee Goel
Sumi Lim
Steve Zimmerman
Ian Woods
David A Prober
Jason Rihel
author_facet Ida L Barlow
Eirinn Mackay
Emily Wheater
Aimee Goel
Sumi Lim
Steve Zimmerman
Ian Woods
David A Prober
Jason Rihel
author_sort Ida L Barlow
collection DOAJ
description 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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spelling doaj.art-221b77ce3f6641329cfae8555a7e436b2023-08-07T14:09:47ZengeLife Sciences Publications LtdeLife2050-084X2023-08-011210.7554/eLife.87521The zebrafish mutant dreammist implicates sodium homeostasis in sleep regulationIda L Barlow0Eirinn Mackay1Emily Wheater2Aimee Goel3Sumi Lim4Steve Zimmerman5Ian Woods6David A Prober7https://orcid.org/0000-0002-7371-4675Jason Rihel8https://orcid.org/0000-0003-4067-2066Department of Cell and Developmental Biology, University College London, London, United KingdomDepartment of Cell and Developmental Biology, University College London, London, United KingdomDepartment of Cell and Developmental Biology, University College London, London, United KingdomDepartment of Cell and Developmental Biology, University College London, London, United KingdomDepartment of Cell and Developmental Biology, University College London, London, United KingdomDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, United StatesIthaca College, New York, United StatesDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, United StatesDepartment of Cell and Developmental Biology, University College London, London, United KingdomSleep 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.https://elifesciences.org/articles/87521sleepsodium-potassium pumpsleep homeostasiszebrafishgenetic screen
spellingShingle Ida L Barlow
Eirinn Mackay
Emily Wheater
Aimee Goel
Sumi Lim
Steve Zimmerman
Ian Woods
David A Prober
Jason Rihel
The zebrafish mutant dreammist implicates sodium homeostasis in sleep regulation
eLife
sleep
sodium-potassium pump
sleep homeostasis
zebrafish
genetic screen
title The zebrafish mutant dreammist implicates sodium homeostasis in sleep regulation
title_full The zebrafish mutant dreammist implicates sodium homeostasis in sleep regulation
title_fullStr The zebrafish mutant dreammist implicates sodium homeostasis in sleep regulation
title_full_unstemmed The zebrafish mutant dreammist implicates sodium homeostasis in sleep regulation
title_short The zebrafish mutant dreammist implicates sodium homeostasis in sleep regulation
title_sort zebrafish mutant dreammist implicates sodium homeostasis in sleep regulation
topic sleep
sodium-potassium pump
sleep homeostasis
zebrafish
genetic screen
url https://elifesciences.org/articles/87521
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