2. Academic Validation
  3. Ryanodine receptors are part of the myospryn complex in cardiac muscle

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

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.

Figures