Forum for Science, Industry and Business

Discovery of a new heart muscle component: Researchers identify the function of a motor protein

In order for the heart to work properly, it must exert muscular force. This involves the coordinated contraction of numerous sarcomeres, the smallest contractile units of heart muscle. Muscle contraction is brought about by the activity of conventional motor proteins, which pull on thin filaments to shorten sarcomeres.

Transmission electron micrograph of heart muscle. The repeating striped elements represent sarcomeres, and the dark structures represent mitochondria.

WWU Münster - Andreas Unger

Together with researchers from Toronto (Canada) and Leiden (the Netherlands), scientists from the University of Münster have now found out more about the function of a specific unconventional motor protein, myosin 18A (Myo18A): they have discovered a new variant of the protein that appears to be responsible for the assembly and mechanical stability of sarcomeres in the heart.

The results could help scientists better understand how sarcomeres are formed and regulated. The study has been published in “The Journal of Biological Chemistry”, where it was selected as an “Editors’ Pick” and identified as a research highlight.

Background and Method:

It was speculated that the motor protein myosin 18A is important among other things for the motility of cells. But whether, like its “relative” myosin 18B (Myo18B), it also plays a role in the function of heart muscle was unknown until now.

Using gene expression analyses, the scientists observed that the gene coding the protein Myo18A was highly expressed in the heart of mouse embryos. To investigate the function of the protein, the scientists genetically deleted it in developing mice. Global deletion or selective deletion in heart muscle cells was embryonic lethal.

“This means, therefore, that the protein appears to have an important function in the heart”, says biologist Dr. Peter Hanley, group leader at the Institute of Molecular Cell Biology at Münster University.

In cooperation with Dr. Matthias Seidl at the Institute of Pharmacology and Toxicology of the Medical Faculty at Münster University, they found that the previously unknown protein variant Myo18Aγ has a strong presence in the heart – whereas the already known variants Myo18Aα and Myo18β were not detected.

Genetically switching off the newly discovered protein form led to disorganization of the cardiac musculature. This they observed with the help of transmission electron microscopy, which was performed by Dr. Andreas Unger from the Institute of Physiology II of the Medical Faculty at Münster University.

“Our results show that it is not only Myo18B that has a special function in the sarcomere, but also Myo18A”, says Markus Horsthemke, a doctoral student in biology and principal author of the study. The researchers suspect that Myo18A is primarily responsible as a structural protein for the mechanical stabilization of the sarcomere, and is not directly involved in the contraction of heart muscle.

The study is an example of basic research. Whether and when the results will lead to possible applications cannot be predicted at present. The researchers hope in further investigations to decipher exactly how Myo18Aγ regulates the development and function of the sarcomere.

Funding:

The study received financial support from the German Research Foundation, from the Cells-in-Motion Cluster of Excellence at Münster University, and from the Canadian research organizations “Genome Canada” and “Ontario Genomics”.

Wissenschaftliche Ansprechpartner:

PD Dr. Peter Hanley
Institute for Molecular Cell Biology
Schlossplatz 5
48149 Münster
Germany
phone: +49 251 83-23854
hanley@uni-muenster.de

Originalpublikation:

Horsthemke M. et al. (2019): A novel isoform of myosin 18A (Myo18Aγ) is an essential sarcomeric protein in mouse heart. Journal of Biological Chemistry, 2019. DOI: 10.1074/jbc.RA118.004560

Svenja Ronge | idw - Informationsdienst Wissenschaft
Further information:
https://www.uni-muenster.de/

Im Focus: Developing a digital twin

University of Texas and MIT researchers create virtual UAVs that can predict vehicle health, enable autonomous decision-making

In the not too distant future, we can expect to see our skies filled with unmanned aerial vehicles (UAVs) delivering packages, maybe even people, from location...

Im Focus: The coldest reaction

With ultracold chemistry, researchers get a first look at exactly what happens during a chemical reaction

The coldest chemical reaction in the known universe took place in what appears to be a chaotic mess of lasers. The appearance deceives: Deep within that...

Im Focus: How do scars form? Fascia function as a repository of mobile scar tissue

Abnormal scarring is a serious threat resulting in non-healing chronic wounds or fibrosis. Scars form when fibroblasts, a type of cell of connective tissue, reach wounded skin and deposit plugs of extracellular matrix. Until today, the question about the exact anatomical origin of these fibroblasts has not been answered. In order to find potential ways of influencing the scarring process, the team of Dr. Yuval Rinkevich, Group Leader for Regenerative Biology at the Institute of Lung Biology and Disease at Helmholtz Zentrum München, aimed to finally find an answer. As it was already known that all scars derive from a fibroblast lineage expressing the Engrailed-1 gene - a lineage not only present in skin, but also in fascia - the researchers intentionally tried to understand whether or not fascia might be the origin of fibroblasts.

Fibroblasts kit - ready to heal wounds

Im Focus: McMaster researcher warns plastic pollution in Great Lakes growing concern to ecosystem

Research from a leading international expert on the health of the Great Lakes suggests that the growing intensity and scale of pollution from plastics poses serious risks to human health and will continue to have profound consequences on the ecosystem.

In an article published this month in the Journal of Waste Resources and Recycling, Gail Krantzberg, a professor in the Booth School of Engineering Practice...

Im Focus: Machine learning microscope adapts lighting to improve diagnosis

Prototype microscope teaches itself the best illumination settings for diagnosing malaria