CONTACT: JENNIFER CRONIN
2130 Medical Laboratories
Iowa City IA 52242
(319) 335-5661; fax (319) 335-9917
Release: March 4, 1999
UI study reveals important information about molecular defect in
IOWA CITY, Iowa -- For the first time ever, University of Iowa researchers
have confirmed how a protein complex, when defective, causes limb girdle
This information could help scientists to develop new ways to treat
limb girdle forms of muscular dystrophy. Limb girdle varieties affect between
one in 20,000 and one in 50,000 individuals.
"We have established a cell culture system that we can use to mimic
the defect in limb girdle muscular dystrophy," said Kevin Campbell,
Ph.D., UI professor of physiology and biophysics, and neurology, and a
Howard Hughes Medical Institute Investigator.
The UI findings appeared in a recent issue of the Journal of Biological
Campbell, along with Kate Holt, Ph.D., a postdoctoral fellow in Campbell's
lab, used the cell culture system to find out how the protein complex,
called the sarcoglycan complex, forms. The sarcoglycan complex, composed
of four distinct transmembrane glycoproteins, is part of the dystrophin-glycoprotein
complex, a group of proteins located in muscle cell membranes. The dystrophin-glycoprotein
complex is thought to stabilize the membrane against contraction-induced
damage. Past studies have shown that mutations to the sarcoglycan complex
cause various types of limb girdle muscular dystrophy.
Muscular dystrophy is a group of diseases characterized by hereditary
progressive muscle weakness and degeneration. The unifying theme among
limb girdle varieties of the disease is the initial involvement of the
shoulder and pelvic girdle muscles, with relative sparing of most other
Despite rapid advances regarding the genetic defects that cause limb
girdle muscular dystrophy, researchers know little about the molecular
defects underlying the disease. Through their cell culture model, Campbell
and Holt were able to show that complete assembly of the sarcoglycan complex
is dependent on the simultaneous synthesis of all four sarcoglycans. Any
mutant sarcoglycan blocks the complex formation and its insertion into
the plasma membrane. Campbell and Holt's confirmation of how the sarcoglycan
complex develops is a step toward learning more about the basic molecular
underpinnings of the disease.
"If we can determine where the defect or blockage of the biosynthesis
occurs, then that might give us a clue as to a way that we could potentially
treat the disease," Holt said.
One potential treatment could involve developing pharmacological reagents
that would allow proteins with mutations to be properly expressed, Campbell
"We're going to use the model to further study the sarcoglycan
complex," Campbell said. "Now that we can synthesize the complex
in the laboratory, it will be easier to study the function of these proteins
and the molecular pathogenesis of limb girdle muscular dystrophy."