LRS as a Negative Regulator of Muscle Regeneration

Myostatin is perhaps the best known suppressor of muscle growth and regeneration. Myostatin loss of function mutants, both natural and artificial, and in a number of mammalian species, are heavily muscled as a result of differences in regulation of muscle growth. Researchers here report on the discovery of another protein that suppresses muscle regeneration, and which can be targeted to increase the pace and quality of regeneration. This may or may not fall into the same network of regulation as is governed by myostatin, but it is usually the case that any given regulatory system in cellular biochemistry is quite complex and possesses many points at which it can be manipulated. It would not be surprising to find a connection.

Scientists have long studied leucine tRNA-synthetases, or LRS, for its role in protein synthesis. In the last 5-10 years, scientists have begun to realize that LRS and other proteins like it have functions independent of protein synthesis, such as regulation of cell growth. Researchers used mammalian cell cultures and mice in the new study. They compared the speed of muscle repair in mice with normal and lower-than-normal LRS levels. They discovered that mice with lower levels of LRS in their tissues recovered from muscle injury much more quickly than their counterparts with normal LRS levels. A 70% reduction of LRS proteins in the cell does not affect protein synthesis. "But lower levels do positively influence muscle regeneration. We saw that, seven days after injury, the repaired muscle cells are bigger when LRS is lower."

The researchers further unraveled the exact molecular mechanism by which LRS influences muscle regeneration. This led them to hypothesize that a nontoxic inhibitor would block the effect of LRS on muscle cells without interfering with its role in protein synthesis. The inhibitor was shown to work both in mammalian cells and in mice. Muscle repair occurred more rapidly - and the regenerated muscles were stronger - when the inhibitor was present. Researchers are now investigating the effect of LRS on older mice, which tend to rebuild their muscles more slowly and have less muscle tone than younger mice.



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