Washington, Apr 24 : A new study which has found that proper formation of the proteins that power heart and skeletal muscle seem to rely on a precise concentration of a ‘chaperone’ protein known as UNC-45.

The finding may advance understanding heart failure and muscle wasting elsewhere in the body resulting from burns, brain trauma, diabetes, cancer and the effects of aging.
Chaperone proteins guide other newly formed proteins into the shapes that enable them to perform their specific functions.

The study was conducted by a team of researchers let by Dr. Henry Epstein at the University of Texas Medical Branch at Galveston (UTMB).

As part of the study, researchers experimented using tiny worms, of the species Caenorhabiditis elegans, genetically engineered to produce more UNC-45 than normal worms.

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.

A shortage of UNC-45 disrupts myosin formation, leading to muscle paralysis.

Researchers found that an over-supply of UNC-45 is also a problem as it allows the UPS to interfere with myosin assembly. Apparently, being “over-chaperoned” by extra UNC-45 prevents the myosin proteins from binding into thick filaments and leaves them free-floating and vulnerable to the UPS. The result is a partially paralysed worm whose muscles show visibly smaller fibres.

“What we saw was that too much UNC-45 interfered with myosin accumulation and assembly. It now looks as though precise levels of UNC-45 are critical during myosin formation,” Epstein said.
“This kind of process that we’re seeing in our worms is likely to be important in both the building up and tearing down of heart and skeletal muscle in humans. So we predict that the regulation of UNC-45 will be important in heart failure as well as muscle wasting elsewhere in the body, which is significant to people suffering from burns, brain trauma, diabetes, cancer and the effects of aging,” he said.

The findings of the research will be published in the April issue of the Journal of Cell Biology. (ANI)