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A genetic screen identifies dreammist as a regulator of sleep

Barlow, Ida L. and Mackay, Eirinn and Wheater, Emily and Goel, Aimee and Lim, Sumi and Zimmerman, Steve and Woods, Ian and Prober, David A. and Rihel, Jason (2020) A genetic screen identifies dreammist as a regulator of sleep. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20201120-100334059

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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 mutant, dreammist (dmist), with altered sleep-wake dynamics. CRISPR/Cas9-mediated disruption of dmist also led to 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. As intracellular Na+ concentration is disrupted in dmist mutant brains after high neuronal activity similarly to atp1a3a mutants, but is also elevated specifically at night, we propose that sleep-wake stability is modulated by Dmist-dependent changes to Na+ pump function during sleep homeostatic challenge and at specific times of the day-night cycle.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2020.11.18.388736DOIDiscussion Paper
ORCID:
AuthorORCID
Barlow, Ida L.0000-0003-1046-9606
Mackay, Eirinn0000-0003-1436-2259
Wheater, Emily0000-0002-2498-293X
Lim, Sumi0000-0002-1614-9753
Prober, David A.0000-0002-7371-4675
Rihel, Jason0000-0003-4067-2066
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. Version 1 - November 18, 2020; Version 2 - December 6, 2020. The initial screen, discovery, and characterization of dreammist was conducted in the lab of Alexander F Schier at Harvard University. We also would like to thank members of the Rihel lab and other UCL zebrafish groups for helpful comments on experiments and the manuscript over the years. We thank Shannon Shibata-Germanos for fxyd1 mutant tracking experiments, John Parnavalas for reagents, Christine Orengo for help with small peptide sequence searches, Stuart Peirson for early access to mouse transcriptomic data, and Finn Mango Bamber for the Pokémon-card inspired dreammist name. The work was funded by grants awarded to Alexander Schier, R01 GM085357 and HL10952505; an ERC Starting Grant (#282027) and Wellcome Trust Investigator Award (#217150/Z/19/Z) to JR; National Institutes of Health grant NS101158 to DAP; and a Grand Challenges PhD studentship to ILB. The authors have declared no competing interest.
Funders:
Funding AgencyGrant Number
NIHR01 GM085357
NIHHL10952505
European Research Council (ERC)282027
Wellcome Trust217150/Z/19/Z
NIHNS101158
Grand Challenges PhD StudentshipUNSPECIFIED
Record Number:CaltechAUTHORS:20201120-100334059
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201120-100334059
Official Citation:A genetic screen identifies dreammist as a regulator of sleep. Ida L Barlow, Eirinn Mackay, Emily Wheater, Aimee Goel, Sumi Lim, Steve Zimmerman, Ian Woods, David A Prober, Jason Rihel. bioRxiv 2020.11.18.388736; doi: https://doi.org/10.1101/2020.11.18.388736
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:106756
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:20 Nov 2020 19:02
Last Modified:07 Dec 2020 21:09

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