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Ryanodine receptors are part of the myospryn complex in cardiac muscle

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posted on 2023-06-09, 14:46 authored by Matthew Benson, Caroline Tinsley, Aidan Waite, Francesca Carlisle, Steve Sweet, Elisabeth Ehler, Christopher George, Anthony Lai, Enca Martin-Rendon, Derek Blake
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Scientific Reports

ISSN

2045-2322

Publisher

Nature Publishing Group

Issue

6312

Volume

7

Page range

1-12

Department affiliated with

  • Biochemistry Publications

Research groups affiliated with

  • Genome Damage and Stability Centre Publications
  • Sussex Drug Discovery Centre Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2018-08-30

First Open Access (FOA) Date

2018-08-30

First Compliant Deposit (FCD) Date

2018-08-30

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