Findings could improve genetic screening for dangerous muscle diseases.
Scientists have worked out the structure and role of an essential protein that holds our muscles together – alpha-actinin – according to new research published in the journal Cell, part-funded by the British Heart Foundation (BHF).
Alpha-actinin is involved in many processes in the body and is closely related to diseases of the heart muscle, or cardiomyopathies, which can lead to shortness of breath, irregular heartbeat and even death, often in seemingly healthy people.
This research shows how damaged alpha-actinin, caused by a faulty gene, could potentially be identified by screening the family members of those affected by certain cardiomyopathies. The researchers hope that this discovery will also improve screening and lead to treatments for some types of muscular dystrophy.
The results will also allow researchers to assess the impact of other gene defects on the function of alpha-actinin.
The international research team, led by BHF Professor Mathias Gautel at King's College London (KCL) and Professor Kristina Djinović-Carugo at the Max F. Perutz Laboratories (MFPL) of the University of Vienna, used the new structure to study exactly how muscle fibres are held together and, by altering the protein's structure, they were able to examine what happens when alpha-actinin is faulty.
In order to move, our muscles need to be striated – made up of layers. These can be seen as stripes under a microscope. Thousands and thousands of these layers are required to contract when our heart muscle beats and, if these layers are not formed correctly, then serious heart problems can occur.
Alpha-actinin is one of the proteins that holds muscle layers together and spaces them out correctly so that they can withstand the constant contraction and relaxation required for our hearts to continually beat. These new findings show that when the gene that controls alpha-actinin is not working properly, heart muscle does not form regular layers when grown in the lab.
BHF Professor of Molecular Cardiology, Mathias Gautel from King's College London, explains:
"We have worked out the structure of a major protein responsible for muscle layering. This gave us new insights into how muscle is built and how its movement is controlled. We hope that this will help geneticists make accurate diagnoses of muscle diseases and may ultimately lead to designing new therapies."
Professor Kristina Djinović-Carugo from the Max F. Perutz Laboratories (MFPL) in Vienna said:
"It took us eight years to complete our analysis of the protein, alpha-actinin, and to understand the way muscle development is affected when this protein isn't working correctly. This could have future implications in many muscle diseases and underscores the value of funding long-term research. "
Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, which helped fund the research, said:
"This detailed research explains how an essential protein is responsible for the muscle structure of the heart and how, when faulty, it can lead to diseases of the heart muscle known as cardiomyopathies.
"There is currently no cure or treatment for cardiomyopathy and these findings demonstrate the value of funding laboratory research to answer fundamental questions that could ultimately lead to treatments for patients."
The research team included scientists from the Max F. Perutz Laboratories of the University of Vienna, King's College London BHF Centre for Research Excellence, University of Ljubljana, EMBL, the Norwegian University of Science and Technology, the University of Natural Resources and Life Sciences in Vienna, Freie Universität Berlin and was funded by the British Heart Foundation, the Leducq Foundation, the Austrian Science Fund (FWF), the Austrian Research Promotion Agency (FFG), and the EU-FP7 Marie Curie Initial Training Networks initiative.