Compensatory ion transport buffers daily protein rhythms to regulate osmotic balance and cellular physiology.
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Authors
Guna, Alina
Inglis, Alison J
Putker, Marrit
Bartolami, Eline
Matile, Stefan
Lequeux, Nicolas
Voorhees, Rebecca M
Edgar, Rachel S
Publication Date
2021-10-15Journal Title
Nature communications
ISSN
2041-1723
Volume
12
Issue
1
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Stangherlin, A., Watson, J. L., Wong, D. C. S., Barbiero, S., Zeng, A., Seinkmane, E., Chew, S. P., et al. (2021). Compensatory ion transport buffers daily protein rhythms to regulate osmotic balance and cellular physiology.. Nature communications, 12 (1) https://doi.org/10.1038/s41467-021-25942-4
Abstract
Between 6-20% of the cellular proteome is under circadian control and tunes mammalian cell function with daily environmental cycles. For cell viability, and to maintain volume within narrow limits, the daily variation in osmotic potential exerted by changes in the soluble proteome must be counterbalanced. The mechanisms and consequences of this osmotic compensation have not been investigated before. In cultured cells and in tissue we find that compensation involves electroneutral active transport of Na<sup>+</sup>, K<sup>+</sup>, and Cl<sup>-</sup> through differential activity of SLC12A family cotransporters. In cardiomyocytes ex vivo and in vivo, compensatory ion fluxes confer daily variation in electrical activity. Perturbation of soluble protein abundance has commensurate effects on ion composition and cellular function across the circadian cycle. Thus, circadian regulation of the proteome impacts ion homeostasis with substantial consequences for the physiology of electrically active cells such as cardiomyocytes.
Sponsorship
RCUK | Medical Research Council (MC_UP_1201/4)
Wellcome Trust (208790/Z/17/Z)
Medical Research Council (MC_UP_1201/4)
Identifiers
PMC8520019, 34654800
External DOI: https://doi.org/10.1038/s41467-021-25942-4
This record's URL: https://www.repository.cam.ac.uk/handle/1810/330847
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