Peer review process
Not revised: This Reviewed Preprint includes the authors’ original preprint (without revision), an eLife assessment, and public reviews.
Read more about eLife’s peer review process.Editors
- Reviewing EditorYing-Hui FuUniversity of California, San Francisco, San Francisco, United States of America
- Senior EditorDidier StainierMax Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
Joint Public Review:
Barlow et al performed a viral insertion screen in larval zebrafish for sleep mutants. They identify a mutant named dreammist (dmist) that displayed defects in sleep, namely, decreased sleep both day and night, accompanied by increased activity. They find that dmist encodes a previously uncharacterized single-pass transmembrane protein that shows structural similarity to Fxyd1, a Na+K+-ATPase regulator. They go on to show that genetic manipulations of either FXYD1 or the Na/K pump also reduce sleep. They use pharmacology and sleep deprivation experiments to provide further evidence that the NA/K pump regulates intracellular sodium and rebound sleep.
This study provides additional evidence for the important role of membrane excitability in sleep regulation. The conclusions of this paper are mostly well supported by data, with the following strengths and weaknesses as described below.
Strengths:
Elegant use of CRISPR knockout methods to disrupt multiple genes that help establish the importance of regulating Na+K+-ATPase function in sleep.
Data are mostly clearly presented.
Double mutant analysis of dmist and atp1a3a help establish an epistatic relationship between these proteins.
Weaknesses:
The authors emphasize the role of increased cellular sodium. It will be interesting to also see the consequences of perturbating potassium. The potassium channel shaker has been previously identified as a critical sleep regulator in Drosophila.
