Faculty Collaboration Database

Myospryn is a direct transcriptional target for MEF2A that encodes a striated muscle, alpha-actinin-interacting, costamere-localized protein. J Biol Chem 2006 Mar 10;281(10):6841-9

Date

01/13/2006

Pubmed ID

16407236

DOI

10.1074/jbc.M510499200

Scopus ID

2-s2.0-33646559605 (requires institutional sign-in at Scopus site)   44 Citations

Abstract

The full repertoire of proteins that comprise the striated muscle Z-disc and peripheral structures, such as the costamere, have yet to be discovered. Recent studies suggest that this elaborate protein network, which acts as a structural and signaling center for striated muscle, harbors factors that function as mechanosensors to ensure coordinated contractile activity. Mutations in genes whose products reside in this region often result in skeletal and cardio myopathies, demonstrating the importance of this macromolecular complex in muscle structure and function. Here, we describe the characterization of a direct, downstream target gene for the MEF2A transcription factor encoding a large, muscle-specific protein that localizes to the costamere in striated muscle. This gene, called myospryn, was identified by microarray analysis as a transcript down-regulated in MEF2A knock-out mice. MEF2A knock-out mice develop cardiac failure during the perinatal period with mutant hearts exhibiting several cardiac abnormalities including myofibrillar disarray. Myospryn is the mouse ortholog of a partial human cDNA of unknown function named cardiomyopathy-associated gene 5 (CMYA5). Myospryn is expressed as a single, large transcript of approximately 12 kilobases in adult heart and skeletal muscle with an open reading frame of 3739 amino acids. This protein, belonging to the tripartite motif superfamily of proteins, contains a B-box coiled-coil (BBC), two fibronectin type III (FN3) repeats, and SPRY domains and interacts with the sarcomeric Z-disc protein, alpha-actinin-2. Our findings demonstrate that myospryn functions directly downstream of MEF2A at the costamere in striated muscle potentially playing a role in myofibrillogenesis.

Author List

Durham JT, Brand OM, Arnold M, Reynolds JG, Muthukumar L, Weiler H, Richardson JA, Naya FJ

MESH terms used to index this publication - Major topics in bold

Actinin
Animals
Base Sequence
COS Cells
Carrier Proteins
Humans
Intracellular Signaling Peptides and Proteins
MEF2 Transcription Factors
Mice
Mice, Knockout
Mice, Transgenic
Molecular Sequence Data
Muscle Proteins
Muscle, Skeletal
Myocardium
Myogenic Regulatory Factors
Oligonucleotide Array Sequence Analysis
Promoter Regions, Genetic
Sarcomeres