Ryanodine receptors are part of the myospryn complex in cardiac muscle

  • Sci Rep. 2017 Jul 24;7(1):6312. doi: 10.1038/s41598-017-06395-6.
Matthew A Benson  1 ,  Caroline L Tinsley  2 ,  Adrian J Waite  2 ,  Francesca A Carlisle  2 ,  Steve M M Sweet  3 ,  Elisabeth Ehler  4 ,  Christopher H George  5 ,  F Anthony Lai  5  6 ,  Enca Martin-Rendon  7 ,  Derek J Blake  8
Affiliations
  • 1. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • 2. Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
  • 3. Genome Damage and Stability Centre, University of Sussex, Brighton, UK.
  • 4. Randall Division for Cell and Molecular Biophysics, King's College London, London, UK.
  • 5. Institute of Molecular and Experimental Medicine, Wales Heart Research Institute, Cardiff University, Cardiff, UK.
  • 6. Division of Biomedicine, School of Biosciences, Cardiff University, Cardiff, UK.
  • 7. Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • 8. Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK. [email protected].
PMID: 28740084 DOI: 10.1038/s41598-017-06395-6
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.