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.
Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard
New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University
DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.
Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
15.12.2017 | Power and Electrical Engineering
15.12.2017 | Materials Sciences
15.12.2017 | Life Sciences