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JCI online early table of contents: July 1, 2010
Date:7/1/2010

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AUTHOR CONTACT:
Mark L. Kahn
Department of Medicine and Cardiovascular Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Phone: 215.898.9007; Fax: 215.573.2094; E-mail: markkahn@mail.med.upenn.edu.

View this article at: http://www.jci.org/articles/view/39679?key=953594aa09229ff769cd


MUSCLE BIOLOGY: Understanding how mutant proteins cause muscular dystrophy

Limb-girdle muscular dystrophy type 2A (LGMD2A) is a genetic disease characterized by progressive muscle weakness. Most patients become confined to a wheelchair in their third decade of life. Although LGMD2A is known to be caused by mutations in the gene CAPN3, which controls the generation of the protein p94, how mutant p94 proteins lead to disease has not been determined. Now, a team of researchers, led by Hiroyuki Sorimachi, at the Tokyo Metropolitan Institute of Medical Science, Japan, has determined that in mice, mutant p94 protein that is unable to cleave other proteins (a key function of p94) causes a disease that resembles LGMD2A and is exacerbated by exercise. The exercise-induced muscle degeneration was associated with inefficient relocalization of the mutant p94 protein. The authors therefore conclude that exercise-induced dynamic redistribution of p94 is dependent on its ability to cleave other proteins and essential to protect muscle from degeneration.

TITLE: Dynamic distribution of muscle-specific calpain in mice has a key role in physical-stress adaptation and is impaired in muscular dystrophy

AUTHOR CONTACT:
Hiroyuki Sorimachi
The Tokyo Metropolitan Institute of Medical Science (Rinshoken), Tokyo, Japan.
Phone: 81.3.5316.3277; Fax: 81.3.5316.3613; E-mail: sorimachi-hr@igakuken.or.jp.

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Contact: Karen Honey
press_releases@the-jci.org
734-546-5242
Journal of Clinical Investigation
Source:Eurekalert

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