Ryanodine receptors are part of the myospryn complex in cardiac muscle

Benson, Matthew A., Tinsley, Caroline L., Waite, Adrian, Carlisle, Francesca ORCID: https://orcid.org/0000-0002-9734-113X, Sweet, Steve M. M., Ehler, Elisabeth, George, Christopher, Lai, Francis ORCID: https://orcid.org/0000-0003-2852-8547, Martin-Rendon, Enca and Blake, Derek ORCID: https://orcid.org/0000-0002-5005-4731 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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Abstract

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) Medicine
Publisher:	Nature Publishing Group
ISSN:	2045-2322
Date of First Compliant Deposit:	31 July 2017
Date of Acceptance:	12 June 2017
Last Modified:	24 May 2023 19:12
URI:	https://orca.cardiff.ac.uk/id/eprint/103112

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