University of Queensland scientists have provided insight into the cause of muscle diseases including limb-girdle muscular dystrophy and rippling muscle disease.
Dr Harriet Lo from UQ’s Institute for Molecular Bioscience (IMB) said understanding the underlying cause of disease is crucial for developing therapeutic strategies for human patients.
“Most muscle diseases are late-onset and it was unclear how particular genetic mutations led to different types of muscle disease, and why they appeared later in life,” she said.
“We have discovered the essential role of caveolae, small ‘pockets’ on the surface of our cells, in protecting skeletal muscle during movement.
“We found that skeletal muscle cells have a very large number of caveolae which flatten out and allow the cell to ‘stretch’ during vigorous activity.
“Muscles with defective caveolae cannot stretch, resulting in small tears which prevent the muscle from working properly.
“This damage can accumulate over time and lead to muscle disease.”
The researchers used 3D electron microscopy to study the surface structure of muscle cells, and zebrafish to model how muscles function with different genetic mutations.
They showed that mutations in caveolin or cavin proteins disrupted the formation of caveolae and caused damage that could be reversed by expressing the normal form of the protein.
IMB’s Professor Rob Parton said the research highlights the essential role of caveolae in protecting skeletal muscles during movement.
“It shows that targeting defective caveolae may be the way to treat some muscle diseases,” he said.
Previous research by Professor Parton’s team and others has shown that caveolae regulate cell growth and maintain the balance of fats in the cell.
“Patients with defective caveolae can develop cancer, muscular dystrophy, and cardiovascular disease, and lack fat tissue,” Professor Parton said.
The research was supported by funding bodies including the Australian Cancer Research Foundation, the National Health and Medical Research Council and the National Institutes of Health.
Media: IMB Communications, +61 7 3346 2134, 0418 575 247, communications@imb.uq.edu.au
