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Cell 'anchors' required to prevent muscular dystrophy
Date:1/13/2009

DURHAM, N.C. A protein that was first identified for playing a key role in regulating normal heart rhythms also appears to be significant in helping muscle cells survive the forces of muscle contraction. The clue was a laboratory mouse that seemed to have a form of muscular dystrophy.

A group of proteins called ankyrins, or anchor proteins, were first discovered in human red blood cells by Vann Bennett, M.D. a Howard Hughes Medical Institute investigator and James B. Duke Professor of Cell Biology, Biochemistry, and Neurobiology. Ankyrins are a family of proteins that assist in attaching other proteins to the fragile cell membrane, and in the case of red blood cells, this helps cells resist shearing forces when blood is pumped vigorously throughout the body.

Bennett's team was exploring the function of anchor protein ankyrin-B (ankB) by knocking out gene expression of the gene that makes the protein. They found newborn mice missing ankB had splayed shoulder bones, which stuck out of the animals' backs like wings, rather than lying flat, a symptom of a muscular problem.

"I went back to my pediatric textbook and saw images of people with a form of muscular dystrophy who had splayed shoulder bones," said Bennett, "This opened our eyes to the possibility that, in addition to defects in controlling heart rhythm that we have studied before, the mice might also suffer from muscular dystrophy."

The team turned its attention to ankB with regard to muscle cell organization. They knew that people with Duchenne muscular dystrophy were missing the protein dystrophin, and that dystrophin is needed for a protein complex to form and protect the cells' thin plasma-membrane layer from forces exerted by muscle cells contracting.

"Without dystrophin, you lose the entire protective complex, but nobody knew why," Bennett said. "We have found the outlines of a pathway through which dystrophin assembled this complex. The missing piece o
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Contact: Mary Jane Gore
mary.gore@duke.edu
919-660-1309
Duke University Medical Center
Source:Eurekalert

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