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

f the puzzle was the ankyrin proteins." The work appears in Cell journal.

The protective layer is located at a very particular place on the muscle cell membrane, where costameres, riblike structures, hold the bundled muscle cells together. This is similar to a steel cables attaching to a specific point along a suspension bridge to distribute the forces and keep the flexible bridge intact, Bennett said.

When the protective protein layer isn't present, muscle contraction forces may break the cell membrane, toxins pour in and vital enzymes stream out. The muscle cells die.

The first experiment for the new study asked if the protein dystrophin was found on the cell plasma membrane in the study animals which lacked ankB. It was not.

Beta-dystroglycan, the core component of the dystrophin-glycoprotein complex that is responsible for attaching dystrophin to the muscle membrane, also was missing, which suggested that a loss of ankyrin-B is linked to a loss of at least two key proteins in the cell membrane, Bennett said.

The researchers needed to continue their studies in adult mice with fully formed muscle cells to observe them in action, because muscle cells in culture don't have properly functioning costameres. They knew, however, that knocking out ankyrin-B causes the mice to die soon after birth.

Fortunately, Gai Ayalon, Ph.D., a postdoctoral fellow in the Bennett laboratory, devised a method that let researchers manipulate gene expression in a specific section of adult muscle, rather than in the whole animal. "This development let us look right away at what happened in adult mice when we produced ankyrin loss only in leg muscle," Ayalon said.

Next, they studied what happened when they turned off ankyrin-G (ankG), a different anchor protein, in muscle cells. They found that the cells needed ankG to help dystrophin and beta-dystroglycan stay in place at the costameres.

Ayalon exercised the
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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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