Even though each of these distinct muscular dystrophies is caused by mutations to different sugar-adding proteins, glycosylation of alpha-dystroglycan by LARGE appears to restore the function of alpha-dystroglycan in cells affected by all these diseases.

"The finding that LARGE can restore alpha-dystroglycan function regardless of the type of glycosylation defect is incredibly exciting," Campbell said. "This result may have potential application in the development of therapies for an entire group of muscle diseases."

In the Cell publication, Campbell and his colleagues extended their understanding the interactions between alpha-dystroglycan and LARGE. They determined the molecular details of this interaction and discovered that it is critical for the production of biologically active alpha-dystroglycan, which is necessary to prevent muscle degeneration, a characteristic common to most muscular dystrophies.

Rita Barresi, Ph.D., a research investigator in Campbell's lab, was first author on the Nature Medicine paper, and Motoi Kanagawa, Ph.D., an HHMI postdoctoral fellow in Campbell's lab, and Fumiaki Saito, M.D., a former postdoctoral fellow in Campbell's lab, were joint first authors on the Cell paper. The two research teams, both led by Campbell, included scientists from the Departments of Physiology and Biophysics, Neurology, and Pathology in the UI Carver College of Medicine; The Scripps Research Institute in La Jolla, Calif.; California Pacific Medical Center Research Institute in San Francisco, Calif.; Uppsala University in Sweden; University of Toronto in Ontario, Canada; and the National Center of Neurology and Psychiatry in Tokyo, J
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Contact: Jennifer Brown
jennifer-l-brown@uiowa.edu
319-335-9917
University of Iowa
6-Jun-2004