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An ambulance man for muscle damage
Date:12/18/2007

It does not take much to injure a muscle. Sometimes one sudden, inconsiderate movement does the job. Unfortunately, damaged muscles are not as efficient at repair as other tissues such as bone. Researchers of the European Molecular Biology Laboratorys Mouse Biology Unit (EMBL), Italy, and the Harefield Heart Science Centre of Imperial College London, have now discovered a molecular signal that helps muscle regenerate and protects it from atrophy. In this weeks issue of the Journal of Cell Biology they report that the naturally occurring protein is a promising candidate for new strategies in treating muscle damage and wasting.

Muscle regeneration after injury is complex and requires a coordinated interplay between many different processes. Key players in regeneration are muscle stem cells, so-called satellite cells. They divide and produce many new muscle cells to fix the damage incurred by injury. A crucial regulator of muscle function and repair is a signalling molecule called calcineurin. It is activated by injury and controls the activity of other key proteins involved in differentiation and the response to damage.

Nadia Rosenthal, head of EMBLs Mouse Biology Unit, and her team have now found a naturally occurring version of calcineurin, called CnA1 that is permanently active and uncouples the proteins activity from injury signals. The expression of CnA1, however, is tightly regulated. It is expressed from the same gene as other versions of the calcineurin A subunit that are not permanently active. CnA1 gains its unique properties by a process called RNA splicing. When the gene has been copied from DNA into RNA certain pieces of information are cut out of the RNA molecule and will not make part of the protein. This is why CnA1 lacks a regulatory site that normally represses its activity.

This system allows flexible reaction to muscle injury, says Rosenthal. Permanently active CnA1 is expressed only in proliferating stem cells and
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Contact: Anna-Lynn Wegener
wegener@embl.de
0049-622-138-7452
European Molecular Biology Laboratory
Source:Eurekalert

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