Ryanodine receptors are part of the myospryn complex in cardiac muscle

Benson, Matthew, Tinsley, Caroline, Waite, Aidan, Carlisle, Francesca, Sweet, Steve, Ehler, Elisabeth, George, Christopher, Lai, Anthony, Martin-Rendon, Enca and Blake, Derek (2017) Ryanodine receptors are part of the myospryn complex in cardiac muscle. Scientific Reports, 7 (6312). pp. 1-12. ISSN 2045-2322

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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
Schools and Departments: School of Life Sciences > Biochemistry
Research Centres and Groups: Genome Damage and Stability Centre
Sussex Drug Discovery Centre
Subjects: Q Science > Q Science (General)
Depositing User: Anna Izykowska
Date Deposited: 30 Aug 2018 11:09
Last Modified: 02 Jul 2019 14:45
URI: http://sro.sussex.ac.uk/id/eprint/78269

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