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Unusual protein modification involved in muscular dystrophy, cancer
Date:12/31/2009

With the discovery of a new type of chemical modification on an important muscle protein, a University of Iowa study improves understanding of certain muscular dystrophies and could potentially lead to new treatments for the conditions.

The findings, which appear in the Jan. 1, 2010, issue of the journal Science, may also have implications for detecting metastasizing cancer cells.

After they are initially made, most proteins are modified through the addition of sugar chains, fats or other chemical groups. These modifications can completely change how a protein works and where it is located in the body. Disruption of these modifications can alter protein function, too, and can lead to disease.

The UI study focused on dystroglycan, a cell membrane protein that is disrupted in many forms of muscular dystrophy. Normal dystroglycan is modified with a unique sugar chain that allows the protein to "glue" muscle membranes to the basal lamina -- a tough layer of extracellular proteins. This arrangement reinforces the fragile muscle membrane and prevents small tears that occur naturally from expanding and damaging the membrane.

Recent work, including studies by the UI team, show that disrupting dystroglycan's ability to attach to the basal lamina causes congenital muscular dystrophies and also leads to cancer progression in epithelial cell cancer. In these conditions, the dystroglycan sugar chain is incompletely or incorrectly assembled and the dystroglycan cannot bind tightly to laminin.

"Dystroglycan is a complex and unusual glycoprotein. It is heavily covered with many types of sugars. We wanted to know the shape and make up of the unique sugar chain that allows dystroglycan to bind to laminin," said study leader Kevin Campbell, Ph.D., professor and head of molecular physiology and biophysics at the UI Roy J. and Lucille A. Carver College of Medicine and a Howard Hughes Medical Institute investigator.

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Contact: Jennifer Brown
jennifer-l-brown@uiowa.edu
319-356-7124
University of Iowa
Source:Eurekalert

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