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

Compensatory ion transport buffers daily protein rhythms to regulate osmotic balance and cellular physiology.
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DOI:
10.1038/s41467-021-25942-4
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发表时间:
2021-10-15
影响因子:
16.6
通讯作者:
O'Neill JS
O'Neill JS
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Stangherlin A;Watson JL;Wong DCS;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

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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. Osmotic compensation by electroneutral ion transport buffers TORC1-mediated changes in the cytosolic proteome, and maintains intracellular homeostasis and cell volume over the circadian cycle. Here, the authors find such ion content changes drive daily rhythms in cardiomyocyte electrical activity.
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