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Researchers find level of special protein is critical to proper formation of muscles

GALVESTON, Texas -- Proper formation of the proteins that power heart and skeletal muscle seems to rely on a precise concentration of a "chaperone" protein known as UNC-45, according to a new study.

This basic discovery may have important implications for understanding and eventually treating heart failure and muscle wasting elsewhere in the body resulting from burns, brain trauma, diabetes, cancer and the effects of aging, the senior author of the paper said. The finding resulted from experiments using tiny, genetically engineered worms at the University of Texas Medical Branch at Galveston (UTMB), and is reported in a paper featured on the cover of the April 23, 2007, issue of the Journal of Cell Biology.

Chaperone proteins (known to biologists simply as chaperones) guide other newly formed proteins into the shapes that enable them to perform their specific functions.

In muscle cells, UNC-45 acts as a chaperone for myosin proteins, helping them fold into long, thin stable structures which clump together to form the thicker filaments that give heart and skeletal muscle its striated appearance. Chemical signals cause these myosin filaments to contract -- producing a heartbeat, for example, or an arm movement.

Scientists already knew that a shortage of UNC-45 disrupted myosin formation, leading to muscle paralysis. The reason: when there's not enough UNC-45 to go around, myosin proteins not yet in their final, stable form fall victim to a cellular cleanup squad called the ubiquitin/proteasome system (UPS), which breaks unstable (and presumably malfunctioning) proteins down into their amino acid components.

But the UTMB study, done using worms of the species Caenorhabiditis elegans (also known as C. elegans), showed that an over-supply of UNC-45 is also a problem.

"What we saw was that too much UNC-45 interfered with myosin accumulation and assembly," said Dr. Henry Epstein, chairman of UTMB's Department o
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Contact: Jim Kelly
jpkelly@utmb.edu
409-772-8791
University of Texas Medical Branch at Galveston
23-Apr-2007


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