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Ryanodine receptors are part of the myospryn complex in cardiac muscle

Benson, Matthew A., Tinsley, Caroline L., Waite, Adrian, Carlisle, Francesca, Sweet, Steve M. M., Ehler, Elisabeth, George, Christopher, Lai, Francis, Martin-Rendon, Enca and Blake, Derek 2017. Ryanodine receptors are part of the myospryn complex in cardiac muscle. Scientific Reports 7 (1) , 6312. 10.1038/s41598-017-06395-6

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The Cardiomyopathy–associated gene 5 (Cmya5) encodes myospryn, a large tripartite motif (TRIM)-related protein found predominantly in cardiac and skeletal muscle. Cmya5 is an expression biomarker for a number of diseases affecting striated muscle and may also be a schizophrenia risk gene. To further understand the function of myospryn in striated muscle, we searched for additional myospryn paralogs. Here we identify a novel muscle-expressed TRIM-related protein minispryn, encoded by Fsd2, that has extensive sequence similarity with the C-terminus of myospryn. Cmya5 and Fsd2 appear to have originated by a chromosomal duplication and are found within evolutionarily-conserved gene clusters on different chromosomes. Using immunoaffinity purification and mass spectrometry we show that minispryn co-purifies with myospryn and the major cardiac ryanodine receptor (RyR2) from heart. Accordingly, myospryn, minispryn and RyR2 co-localise at the junctional sarcoplasmic reticulum of isolated cardiomyocytes. Myospryn redistributes RyR2 into clusters when co-expressed in heterologous cells whereas minispryn lacks this activity. Together these data suggest a novel role for the myospryn complex in the assembly of ryanodine receptor clusters in striated muscle.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Biosciences
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Nature Publishing Group
ISSN: 2045-2322
Date of First Compliant Deposit: 31 July 2017
Date of Acceptance: 12 June 2017
Last Modified: 11 Dec 2020 03:18

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