Navigation Links
Salk scientists hammer out a pathway that promotes muscle cell survival in mice

Scientists at the Salk Institute for Biological Studies have identified an enzyme that pumps up a cell’s ability to maintain healthy muscle and restores normal muscle function in genetically engineered mice with weak muscles. The study, published online in Nature Medicine, is the first to explore the part this enzyme plays in a cascade of events triggered by exercise-induced hormones and other signals.

In this particular pathway, a molecular switch turns on a set of muscle-specific genes in response to exercise by releasing a brake that normally keeps these genes off. Learning how this pathway affects cellular responses may provide clues for improving cellular health in diseases affecting muscle and other cell types.

"In addition to muscle, this regulatory circuit is present in brain and heart tissue, where it also seems to control cell survival," said Marc Montminy, M.D., Ph.D., professor in the Clayton Foundation Laboratories for Peptide Biology at the Salk Institute and senior author of the study. "Therefore, we believe that understanding the role of this enzyme in muscle cells may someday shed light on the underlying mechanisms of many diseases that affect cell survival, such as muscular dystrophy, neurodegenerative diseases, and congestive heart failure."

Montminy’s team, led by postdoctoral researcher Rebecca Berdeaux, Ph.D., first became interested in the enzyme when they observed that mice engineered to have a defect in a molecular switch, called cAMP responsive element binding protein (CREB), had hunched backs, muscle wasting, and other signs of unhealthy muscles. Although CREB had long been studied for its role in glucose regulation in metabolic tissues like the liver and pancreas, its function in muscle tissue was unknown. Then, the researchers noticed that mice lacking CREB activity in their muscle cells also had a genetic brake, called histone deacetylase (HDAC), stuck in place. Without loosening the brake by a chemical mod ification process known as phosphorylation, muscle-specific genes could not be activated and the mice lacked proper muscle function.

In order to determine how CREB acts to regulate HDAC, Berdeaux and colleagues looked for phosphorylation sites in the HDAC protein. They discovered that one of many proteins turned on and off by the CREB switch, a little-known enzyme called salt-inducible kinase-1, or SIK1, specifically recognizes and phosphorylates HDAC.

Then, to explore the possibility that SIK1 is the enzyme controlling the HDAC brake in muscle cells, the researchers reduced SIK1 activity in muscle cells grown in the lab using a technique that silences gene expression. Less SIK1 activity resulted in less phosphorylated HDAC. With the unphosphorylated HDAC brake now firmly in place, expression of muscle-specific target genes was also reduced. Conversely, when the researchers boosted SIK1 levels or inhibited HDAC activity with a drug, muscle cell health was restored in mice genetically engineered to lack CREB and suffering from muscle weakness as a result.

"We’ve discovered that SIK1 provides a completely unexpected link between two important mechanisms of gene regulation, CREB and HDAC, and have shown that this pathway plays a major role in maintaining normal muscle function," said Berdeaux. "Now it remains to be seen how this pathway works in muscle under different conditions, such as during exercise, as well as what part it plays in maintaining cell survival in other tissue types and in other species."

Indeed, all mammals have SIK1, not just mice, and even worms and fruit flies use variations of the enzyme. And as Montminy adds, "Application of this same pathway over and over across species further emphasizes its importance."

Source:Salk Institute

Related biology news :

1. Wisconsin scientists grow critical nerve cells
2. UCSB scientists probe sea floor venting to gain understanding of early life on Earth
3. UAB scientists discover the origin of a mysterious physical force
4. Fox Chase Cancer Center scientists identify immune-system mutation
5. Weizmann Institute scientists develop a new approach for directing treatment to metastasized prostate cancer in the bones.
6. U-M scientists find genes that control growth of common skin cancer
7. UCLA scientists transform HIV into cancer-seeking missile
8. RNA project to create language for scientists worldwide
9. Carnegie Mellon scientists develop tool that uses MRI to visualize gene expression in living animals
10. To control germs, scientists deploy tiny agents provocateurs
11. Leprosy microbes lead scientists to immune discovery

Post Your Comments:

(Date:6/2/2016)... 2016 Perimeter Surveillance & Detection ... Physical Infrastructure, Support & Other Service  The ... offers comprehensive analysis of the global Border Security ... revenues of $17.98 billion in 2016. Now: ... leader in software and hardware technologies for advanced video ...
(Date:5/20/2016)... , May 20, 2016  VoiceIt is excited ... with VoicePass. By working together, VoiceIt ...  Because VoiceIt and VoicePass take slightly different approaches ... increases both security and usability. ... about this new partnership. "This marketing ...
(Date:5/9/2016)... Elevay is currently known as ... for high net worth professionals seeking travel for work ... world, there is still no substitute for a face-to-face ... your deal with a firm handshake. This is why ... of citizenship via investment programs like those offered by ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... Houston Methodist Willowbrook Hospital has signed ... to serve as their official health care provider. ... will provide sponsorship support, athletic training services, and ... volunteers, athletes and families. "We are ... and to bring Houston Methodist quality services and ...
(Date:6/23/2016)... , June 23, 2016   EpiBiome , a ... $1 million in debt financing from Silicon Valley Bank ... automation and to advance its drug development efforts, as ... facility. "SVB has been an incredible strategic ... services a traditional bank would provide," said Dr. ...
(Date:6/23/2016)... , June 23, 2016 Apellis Pharmaceuticals, ... 1 clinical trials of its complement C3 inhibitor, ... and multiple ascending dose studies designed to assess ... of subcutaneous injection in healthy adult volunteers. ... either as a single dose (ranging from 45 ...
(Date:6/23/2016)... ... June 23, 2016 , ... ClinCapture, the only free ... and will showcase its product’s latest features from June 26 to June 30, ... poster on Disrupting Clinical Trials in The Cloud during the conference. DIA ...
Breaking Biology Technology: