Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Muscle atrophy through thick but not thin

09.06.2009
Ubiquitylating enzyme MuRF1 targets thick fibers in muscle

During desperate times, such as fasting, or muscle wasting that afflicts cancer or AIDS patients, the body cannibalizes itself, atrophying and breaking down skeletal muscle proteins to liberate amino acids.

In a new study published online June 8 and in the June 15, 2009 print issue of the Journal of Cell Biology (www.jcb.org), Shenhav Cohen, Alfred Goldberg, and colleagues show that muscle atrophy is a more ordered process than was previously thought. These researchers find evidence that enzyme MuRF1 selectively degrades the thick filaments in muscle, while bypassing the thin filaments.

We depend on skeletal muscles because they can produce movement, but they serve another purpose too. "Skeletal muscle is a protein reservoir that can be mobilized in times of need," says Goldberg. The structural core of a muscle cell is the myofibril, composed of myosin-containing thick filaments and actin-containing thin filaments. During atrophy, this structure is disassembled, but exactly how was not known. MuRF1, an atrophy-related gene, is a ubiquitin ligase that "ubiquitylates," or tags a protein, by attaching a ubiquitin molecule, marking it for degradation by the cell. It was unclear when and how ubiquitylation was involved in disassembling skeletal muscles. The researchers triggered atrophy in mice containing defective MuRF1 (lacking its RING-finger domain crucial for ubiquitylation). These mutant mice break down less muscle than wild-type mice, and less ubiquitylation takes place in the mutants.

Cohen and colleagues found that MuRF1 targets the thick filament, demolishing various components in a specific order. The researchers hypothesize that removal of certain thick filament components first permits subsequent MuRF1 access to the myosin heavy chain. However, MuRF1 doesn't exert the same power over the thin filament, which began to come apart even when MuRF1 was absent.

"Up to now, people thought the muscle just gets smaller" during atrophy, Goldberg says. Instead, these findings paint a picture of a well-regulated process of degradation and disassembly. This mechanism "allows the muscle to still be a muscle and function," Goldberg says. "Atrophy doesn't just destroy muscle cells, like apoptosis." The results indicate that MuRF1 doesn't have to wait for caspases or calpains to "pre-digest" the myofibril components. The work also bears on the practical question of whether atrophy can be halted or reversed with drugs. "It argues against MuRF1 inhibitors" for this purpose, Goldberg says, because the enzyme is responsible for degrading only some muscle components, whereas others fall victim to other ubiquitin ligases and autophagy. Inhibitors that work upstream to block signals that activate ubiquitin ligases and initiate autophagy are a better bet.

About the Journal of Cell Biology

Founded in 1955, the Journal of Cell Biology (JCB) is published by the Rockefeller University Press. All editorial decisions on manuscripts submitted are made by active scientists in conjunction with our in-house scientific editors. JCB content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works and third parties may reuse the content for non-commercial purposes under a creative commons license. For more information, please visit www.jcb.org or visit the JCB press release archive at http://www.eurekalert.org/jrnls/rupress.

Cohen, S., et al. 2009. J. Cell Biol. doi:10.1083/jcb.200901052.

Rita Sullivan | EurekAlert!
Further information:
http://www.rupress.org
http://www.jcb.org

More articles from Life Sciences:

nachricht Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology

nachricht Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Bare bones: Making bones transparent

27.04.2017 | Life Sciences

Study offers new theoretical approach to describing non-equilibrium phase transitions

27.04.2017 | Physics and Astronomy

From volcano's slope, NASA instrument looks sky high and to the future

27.04.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>