"Injecting the protein helped us prove that glycosylated dystroglycan is required to attach the membrane to the extracellular proteins and thus reinforce the membrane integrity," said Campbell, who also holds the Roy J. Carver Chair of Physiology and Biophysics. "However, this tool also suggests that delivering functional dystroglycan to muscles may be a possible therapeutic approach for treating these muscular dystrophies."
Another experiment, which also confirmed the role of glycosylated dystroglycan in binding the membrane and the basal lamina, also may have clinical implications.
The team showed that a virus called LCMV (Lymphocytic Choriomeningitis virus), which binds tightly to alpha dystroglycan, also disrupts the basal lamina muscle membrane interaction and compromises the integrity of the muscle membranes. LCMV is a member of a group of viruses that can cause hemorrhagic diseases. The study suggests that these viruses disrupt the dystroglycan basal lamina interaction, rendering the cell membrane susceptible to rupture.
"Considering how essential cell membranes are for life, these barriers are remarkably fragile. In addition, many tissues, including muscle, GI tract and skin, are constantly under mechanical stress, which can rupture cell membranes," Campbell said. "Our findings support the idea that reinforcement of the membrane basal lamina attachment is a basic cellular mechanism that allows cell survival in tissues subjected to mechanical stress."
|Contact: Jennifer Brown|
University of Iowa