Ryanodine receptors are part of the myospryn complex in cardiac muscle.
Matthew A BensonCaroline L TinsleyAdrian J WaiteFrancesca A CarlisleSteve M M SweetElisabeth EhlerChristopher H GeorgeF Anthony LaiEnca Martin-RendonDerek J BlakePublished in: Scientific reports (2017)
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.
Keyphrases
- skeletal muscle
- copy number
- mass spectrometry
- left ventricular
- genome wide
- heart failure
- insulin resistance
- induced apoptosis
- poor prognosis
- bipolar disorder
- electronic health record
- liquid chromatography
- high resolution
- atrial fibrillation
- oxidative stress
- gene expression
- type diabetes
- signaling pathway
- cell death
- endothelial cells
- artificial intelligence
- data analysis
- saccharomyces cerevisiae
- cell cycle arrest