Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Myosin accumulation and striated muscle myopathy result from the loss of muscle RING finger 1 and 3

[img] PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB

Item Type:Article
Title:Myosin accumulation and striated muscle myopathy result from the loss of muscle RING finger 1 and 3
Creators Name:Fielitz, J. and Kim, M.S. and Shelton, J.M. and Latif, S. and Spencer, J.A. and Glass, D.J. and Richardson, J.A. and Bassel-Duby, R. and Olson, E.N.
Abstract:Maintenance of skeletal and cardiac muscle structure and function requires precise control of the synthesis, assembly, and turnover of contractile proteins of the sarcomere. Abnormalities in accumulation of sarcomere proteins are responsible for a variety of myopathies. However, the mechanisms that mediate turnover of these long-lived proteins remain poorly defined. We show that muscle RING finger 1 (MuRF1) and MuRF3 act as E3 ubiquitin ligases that cooperate with the E2 ubiquitin-conjugating enzymes UbcH5a, -b, and -c to mediate the degradation of beta/slow myosin heavy chain (beta/slow MHC) and MHCIIa via the ubiquitin proteasome system (UPS) in vivo and in vitro. Accordingly, mice deficient for MuRF1 and MuRF3 develop a skeletal muscle myopathy and hypertrophic cardiomyopathy characterized by subsarcolemmal MHC accumulation, myofiber fragmentation, and diminished muscle performance. These findings identify MuRF1 and MuRF3 as key E3 ubiquitin ligases for the UPS-dependent turnover of sarcomeric proteins and reveal a potential basis for myosin storage myopathies.
Keywords:DNA-Binding Proteins, Electron Microscopy, Heart Diseases, Muscular Diseases, Myosins, Polycomb Repressive Complex 1, Protein Binding, Protein-Serine-Threonine Kinases, Ubiquitin, Animals, Mice
Source:Journal of Clinical Investigation
ISSN:0021-9738
Publisher:American Society for Clinical Investigation (U.S.A.)
Volume:117
Number:9
Page Range:2486-2495
Date:September 2007
Official Publication:https://doi.org/10.1172/JCI32827
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library