Once opened, ryanodine receptors (RyR) are efficient pathways for the release of Ca2+ from the endoplasmic/sarcoplasmic reticulum (ER/SR). The precise nature of the Ca2+-release event, however, requires fine-tuning for the specific process and type of cell involved. For example, the spatial organization of RyRs, the luminal [Ca2+] and the influence of soluble regulators that fluctuate under physiological and pathophysiological control mechanisms, all affect the amplitude and duration of RyR Ca2+ fluxes. Various proteins are docked tightly to the huge bulky structure of RyR and there is growing evidence that, together, they provide a sophisticated and integrated system for regulating RyR channel gating. This review focuses on those proteins that are relevant to phosphorylation of RyR channels with particular reference to the cardiac isoform of RyR (RyR2). How phosphorylation of RyR affects channel activity and whether proteins such as the FK-506 binding proteins (FKBP12 and FKBP12.6) are involved, have been highly controversial subjects for more than a decade. But that is expected given the large number of participating proteins, the relevance of phosphorylation in heart failure and inherited arrhythmic diseases, and the frustrations of predicting relationships between structure and function before the advent of a high resolution structure of RyR.
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June 2015
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Conference Article|
June 01 2015
The ryanodine receptor provides high throughput Ca2+-release but is precisely regulated by networks of associated proteins: a focus on proteins relevant to phosphorylation
Fiona O'Brien;
Fiona O'Brien
*Department of Pharmacology, University of Oxford, Oxford OX1 3QT, U.K.
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Elisa Venturi;
Elisa Venturi
*Department of Pharmacology, University of Oxford, Oxford OX1 3QT, U.K.
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Rebecca Sitsapesan
Rebecca Sitsapesan
1
*Department of Pharmacology, University of Oxford, Oxford OX1 3QT, U.K.
1To whom correspondence should be addressed (emailrebecca.sitsapesan@pharm.ox.ac.uk).
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Publisher: Portland Press Ltd
Received:
December 12 2014
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2015 Biochemical Society
2015
Biochem Soc Trans (2015) 43 (3): 426–433.
Article history
Received:
December 12 2014
Citation
Fiona O'Brien, Elisa Venturi, Rebecca Sitsapesan; The ryanodine receptor provides high throughput Ca2+-release but is precisely regulated by networks of associated proteins: a focus on proteins relevant to phosphorylation. Biochem Soc Trans 1 June 2015; 43 (3): 426–433. doi: https://doi.org/10.1042/BST20140297
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