It does not take much to injure a muscle. Sometimes one sudden, inconsiderate movement does the job. Unfortunately, damaged muscles are not as efficient at repair as other tissues such as bone. Researchers of the European Molecular Biology Laboratory’s Mouse Biology Unit (EMBL), Italy, and the Harefield Heart Science Centre of Imperial College London, have now discovered a molecular signal that helps muscle regenerate and protects it from atrophy. In this week’s issue of the Journal of Cell Biology they report that the naturally occurring protein is a promising candidate for new strategies in treating muscle damage and wasting.
Muscle regeneration after injury is complex and requires a coordinated interplay between many different processes. Key players in regeneration are muscle stem cells, so-called satellite cells. They divide and produce many new muscle cells to fix the damage incurred by injury. A crucial regulator of muscle function and repair is a signalling molecule called calcineurin. It is activated by injury and controls the activity of other key proteins involved in differentiation and the response to damage.
Nadia Rosenthal, head of EMBL’s Mouse Biology Unit, and her team have now found a naturally occurring version of calcineurin, called CnAß1 that is permanently active and uncouples the protein’s activity from injury signals. The expression of CnAß1, however, is tightly regulated. It is expressed from the same gene as other versions of the calcineurin Aß subunit that are not permanently active. CnAß1 gains its unique properties by a process called RNA splicing. When the gene has been copied from DNA into RNA certain pieces of information are cut out of the RNA molecule and will not make part of the protein. This is why CnAß1 lacks a regulatory site that normally represses its activity.
“This system allows flexible reaction to muscle injury,” says Rosenthal. “Permanently active CnAß1 is expressed only in proliferating stem cells and regenerating muscles, suggesting it as something like an ambulance man that is called only in response to muscle damage.”
To test the effects of permanent CnAß1 expression Enrique Lara-Pezzi from Rosenthal’s lab overexpessed CnAß1 in muscle cells, and observed increased proliferation of muscle stem cells. Switching off the protein had the opposite effect; stem cells stopped dividing and differentiated into muscle cells instead. When CnAß1 was overexpressed in the muscles of transgenic mice, the animals were resistant to the destructive effects of muscle injury and regenerated the damage more efficiently.
Using sophisticated molecular techniques the scientists revealed that calcineurin accomplishes its effect on muscle by inhibiting another protein called FoxO. FoxO is a transcription factor, a protein that plays a crucial role in skeletal muscle atrophy through the induction of genes involved in cell cycle repression and protein degradation. Suppressing the effects of FoxO, calcineurin ensures that proliferating cells stay alive and keep dividing to produce enough cells to repair muscle damage.
“Supplementary CnAß1 also reduces the formation of scars in damaged muscle, helps speed up the resolution of inflammation and protects muscle cells from atrophy under starvation,” says Rosenthal. “These effects make CnAß1 a promising candidate for new therapeutic approaches against muscle wasting.”
Published on 17 December in Journal of Cell Biology.Anna-Lynn Wegener
Anna-Lynn Wegener | EMBL
Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex
New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center
In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.
Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
22.06.2018 | Materials Sciences
22.06.2018 | Earth Sciences
22.06.2018 | Life Sciences