Navigation Links
Muscle atrophy through thick but not thin
Date:6/8/2009

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.


'/>"/>

Contact: Rita Sullivan
news@rupress.org
212-327-8603
Rockefeller University Press
Source:Eurekalert

Related biology news :

1. Muscle mass: Scientists identify novel mode of transcriptional regulation during myogenesis
2. Pittsburgh scientists identify human source of stem cells with potential to repair muscle
3. Massive microRNA scan uncovers leads to treating muscle degeneration
4. Mechanism for regulation of growth and differentiation of adult muscle stem cells is revealed
5. How molecular muscles help cells divide
6. An ambulance man for muscle damage
7. Stem-cell transplantation improves muscles in MD animal model, UT Southwestern researchers report
8. Long-term use of mechanical ventilation contributes to the deterioration of human diaphragm muscle
9. RING finger protein 5 may guide treatment for muscle disease in older adults
10. Ibuprofen or acetaminophen in long-term resistance training increases muscle mass/strength
11. Pitt and University of Chicago researchers uncover process behind heart muscle contraction
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/20/2017)... 2017 PMD Healthcare announces the release of ... Management System (WMS), a remote, real-time lung health monitoring ... Healthcare is a Medical Device, Digital Health, and Chronic ... creating innovative solutions that empower people to improve their ... PMD developed the first ever personal spirometer, Spiro PD, ...
(Date:3/9/2017)... , Australia , March 9, 2017 ... data at the prestigious World Lung Imaging Workshop at ... Andreas Fouras , was invited to deliver the latest ... medicine. This globally recognised event brings together leaders at ... the latest developments in lung imaging. ...
(Date:3/7/2017)... LAKE CITY , March 7, 2017   ... that help top global companies identify the best talent, ... as Chief Sales Officer (CSO) and Diana ... Kucer,s appointments round out a seasoned executive team poised to ... and beyond, building on a year of record bookings ...
Breaking Biology News(10 mins):
(Date:3/27/2017)... YORK , March 27, 2017 ... developing novel therapies for neurodegenerative diseases, including Alzheimer,s ... that its application to list the Company,s common ... approved by The NASDAQ Stock Market, a unit ... the listing, Neurotrope will ring the Opening Bell at ...
(Date:3/24/2017)... , March 24, 2017  Infectex Ltd., a ... today announced positive results of a Phase 2b-3 clinical ... regimen in patients with multidrug-resistant pulmonary tuberculosis (MDR-TB). SQ109 ... at Sequella, Inc. ( USA ) and ... A total of 140 patients were enrolled in a ...
(Date:3/24/2017)... Biotech Ltd. ("Sinovac" or the "Company") (NASDAQ: SVA), a leading provider ... that its board of directors has amended its shareholder rights plan. The ... 2017 to March 27, 2018. The amendment was not in response to ... ... Ltd. is a China -based biopharmaceutical company that ...
(Date:3/24/2017)... VILLAGE, Calif. , March 24, 2017   ... dermatology and aesthetics company, today announced that Richard ... Officer, effective March 24.   Peterson, who brings ... succeed John Smither , who is retiring at ... Sienna in an advisory capacity. Peterson joins Sienna from ...
Breaking Biology Technology: