Ryanodine receptors are part of the myospryn complex in cardiac muscle

Matthew A. Benson, Caroline L. Tinsley, Adrian J. Waite, Francesca A. Carlisle, Steve M.M. Sweet, Elisabeth Ehler, Christopher H. George, F. Anthony Lai, Enca Martin-Rendon, Derek J. Blake*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)
150 Downloads (Pure)

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.

Original languageEnglish
Article number6312
JournalScientific Reports
Volume7
Issue number1
Early online date24 Jul 2017
DOIs
Publication statusE-pub ahead of print - 24 Jul 2017

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