Compensatory ion transport buffers daily protein rhythms to regulate osmotic balance and cellular physiology

Alessandra Stangherlin; Silvia Barbiero; Aiwei Zeng; Estere Seinkmane; Sew Peak Chew; Andrew D Beale; Edward A Hayter; Alina Guna; Alison J Inglis; Marrit Putker; Eline Bartolami; Stefan Matile; Nicolas Lequeux; Thomas Pons; Jason Day; Gerben van Ooijen; Rebecca M Voorhees; David A Bechtold; Emmanuel Derivery; Rachel S Edgar; Peter Newham; John S O'Neill

doi:10.1038/s41467-021-25942-4

Compensatory ion transport buffers daily protein rhythms to regulate osmotic balance and cellular physiology

Alessandra Stangherlin, Silvia Barbiero, Aiwei Zeng, Estere Seinkmane, Sew Peak Chew, Andrew D Beale, Edward A Hayter, Alina Guna, Alison J Inglis, Marrit Putker, Eline Bartolami, Stefan Matile, Nicolas Lequeux, Thomas Pons, Jason Day, Gerben van Ooijen, Rebecca M Voorhees, David A Bechtold, Emmanuel Derivery, Rachel S EdgarPeter Newham, John S O'Neill

Division of Diabetes, Endocrinology & Gastroenterology (L5)

Research output: Contribution to journal › Article › peer-review

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+, K+, and Cl- 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.

Original language	English
Article number	6035
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-25942-4
Publication status	Published - 15 Oct 2021

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Stangherlin, A., Barbiero, S., Zeng, A., Seinkmane, E., Chew, S. P., Beale, A. D., Hayter, E. A., Guna, A., Inglis, A. J., Putker, M., Bartolami, E., Matile, S., Lequeux, N., Pons, T., Day, J., van Ooijen, G., Voorhees, R. M., Bechtold, D. A., Derivery, E., ... O'Neill, J. S. (2021). Compensatory ion transport buffers daily protein rhythms to regulate osmotic balance and cellular physiology. Nature Communications, 12(1), [6035]. https://doi.org/10.1038/s41467-021-25942-4

@article{18da002dabdb4b11a8886a1edaff67d1,

title = "Compensatory ion transport buffers daily protein rhythms to regulate osmotic balance and cellular physiology",

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+, K+, and Cl- 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.",

author = "Alessandra Stangherlin and Silvia Barbiero and Aiwei Zeng and Estere Seinkmane and Chew, {Sew Peak} and Beale, {Andrew D} and Hayter, {Edward A} and Alina Guna and Inglis, {Alison J} and Marrit Putker and Eline Bartolami and Stefan Matile and Nicolas Lequeux and Thomas Pons and Jason Day and {van Ooijen}, Gerben and Voorhees, {Rebecca M} and Bechtold, {David A} and Emmanuel Derivery and Edgar, {Rachel S} and Peter Newham and O'Neill, {John S}",

note = "Funding Information: We thank Alex Harmer, Helen Causton, and past and present O{\textquoteright}Neill lab members for valuable discussion and contribution, particularly Priya Crosby and Ned Hoyle, visual aids, and the biological services group for assistance with animal work and husbandry. Funding: E.D. was supported by the Medical Research Council (MC_UP_1201/13) and the Human Frontier Science Program (CDA00034/2017-C); RSE by a Wellcome Trust Sir Henry Dale Fellowship (208790/Z/17/Z). This work was supported by the AstraZe-neca Blue Skies Initiative and the Medical Research Council (MC_UP_1201/4). Publisher Copyright: {\textcopyright} 2021, Crown.",

year = "2021",

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doi = "10.1038/s41467-021-25942-4",

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Stangherlin, A, Barbiero, S, Zeng, A, Seinkmane, E, Chew, SP, Beale, AD, Hayter, EA, Guna, A, Inglis, AJ, Putker, M, Bartolami, E, Matile, S, Lequeux, N, Pons, T, Day, J, van Ooijen, G, Voorhees, RM, Bechtold, DA, Derivery, E, Edgar, RS, Newham, P & O'Neill, JS 2021, 'Compensatory ion transport buffers daily protein rhythms to regulate osmotic balance and cellular physiology', Nature Communications, vol. 12, no. 1, 6035. https://doi.org/10.1038/s41467-021-25942-4

TY - JOUR

T1 - Compensatory ion transport buffers daily protein rhythms to regulate osmotic balance and cellular physiology

AU - Stangherlin, Alessandra

AU - Barbiero, Silvia

AU - Zeng, Aiwei

AU - Seinkmane, Estere

AU - Chew, Sew Peak

AU - Beale, Andrew D

AU - Hayter, Edward A

AU - Guna, Alina

AU - Inglis, Alison J

AU - Putker, Marrit

AU - Bartolami, Eline

AU - Matile, Stefan

AU - Lequeux, Nicolas

AU - Pons, Thomas

AU - Day, Jason

AU - van Ooijen, Gerben

AU - Voorhees, Rebecca M

AU - Bechtold, David A

AU - Derivery, Emmanuel

AU - Edgar, Rachel S

AU - Newham, Peter

AU - O'Neill, John S

N1 - Funding Information: We thank Alex Harmer, Helen Causton, and past and present O’Neill lab members for valuable discussion and contribution, particularly Priya Crosby and Ned Hoyle, visual aids, and the biological services group for assistance with animal work and husbandry. Funding: E.D. was supported by the Medical Research Council (MC_UP_1201/13) and the Human Frontier Science Program (CDA00034/2017-C); RSE by a Wellcome Trust Sir Henry Dale Fellowship (208790/Z/17/Z). This work was supported by the AstraZe-neca Blue Skies Initiative and the Medical Research Council (MC_UP_1201/4). Publisher Copyright: © 2021, Crown.

PY - 2021/10/15

Y1 - 2021/10/15

N2 - 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+, K+, and Cl- 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.

AB - 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+, K+, and Cl- 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.

U2 - 10.1038/s41467-021-25942-4

DO - 10.1038/s41467-021-25942-4

M3 - Article

C2 - 34654800

VL - 12

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 6035

ER -

Compensatory ion transport buffers daily protein rhythms to regulate osmotic balance and cellular physiology

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