Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Destructive wizardry of Ozz-E3 ligase appears key to building skeletal muscles in embryos and adults

11.02.2004


Finding mice suggests that abnormalities of this beta-catenin protein underlie certain muscle diseases in human



The organization and stability of growing muscles in both embryonic and adult mice depends on the ability of a protein called Ozz to direct the timely destruction of membrane-bound â-catenin, according to scientists at St. Jude Children’s Research Hospital. â-catenin is one of the key proteins that orchestrates this process. Ozz directs destruction of â-catenin by assembling an active ubiquitin ligase complex, Ozz-E3, which breaks down this pool of the protein in muscle cells.

Ozz-E3’s role is to attach a chain of ubiquitin molecules to â-catenin. This process, called ubiquitination, targets protein substrates for destruction and is essential to many cellular functions during development and adult life.


The researchers also discovered that the Ozz gene overlaps another gene, which codes for an enzyme called protective protein/cathepsin A or PPCA. This enzyme is a key player in a process that breaks down certain molecules in the cellular structure called the lysosome. The Ozz gene also shares with the PPCA gene a genetic "on switch," called a promoter, which controls the expression of either gene, depending on which direction the promoter acts, says Alessandra d’Azzo, Ph.D., a member of Genetics and Tumor Cell Biology at St. Jude. d’Azzo is senior author of a report on these findings that appears in the February issue of Developmental Cell.

"Our finding of the close link between PPCA and Ozz genes might explain why some children with severe neurodegenerative disease caused by mutation of PPCA also suffer from muscle disorders. We are now studying that possibility," d’Azzo said. The St. Jude team made their discoveries using muscle tissue from both normal and genetically modified mice.

The researchers showed that the delicate balance between accumulation and removal of â-catenin at a specific cellular site, the sarcolemma — the membrane covering each muscle fiber — is achieved by the activity of the Ozz-E3 ligase. "Modulating â-catenin levels at the sarcolemma is critical for the organization of sarcomeres, the basic building units of muscle fibers, and, in turn, for the remodeling and the regeneration of skeletal and cardiac muscle," d’Azzo said.

Sarcomeres are composed in large part of two different proteins, actin and myosin. The interaction of actin and myosin pulls the ends of the sarcomere toward each other in a miniature contraction. Thousands of sarcomeres lined up in a row make a myofibril; and large bundles of myofibrils make up a muscle fiber. Muscle fibers work together to form a single muscle, whose ability to contract is based on the accumulated contractions of the many thousands of sarcomeres making up each myofibril.

"For a muscle fiber to grow, there must be a constant rearrangement of myofibrils," d’Azzo said, "and that requires the dynamic removal and replacement of membrane-bound proteins, like â-catenin, that connect the myofibrils to the sarcolemma."

The St. Jude findings indicate that the loss of Ozz function disrupts the correct assembly of sarcomeres, which in turn disrupts muscle formation. Thus, the discovery of the Ozz function during muscle remodeling and growth might help uncover the genetic cause of certain muscle diseases that occur for unknown reason and that affect children in their growing years.

This work was supported in part by NIH, a Cancer Center support grant, Phillip and Elizabeth Gross and ALSAC. d’Azzo holds an endowed chair in Genetics and Gene Therapy from the Jewelers Charity Fund; and A. John Harris was supported by grants from the New Zealand Lottery Board and Foundation for Research Science and Technology.

Other authors of the paper include Tommaso Nastasi, Antonella Bongiovanni, Yvan Campos, Linda Mann, James N. Toy, Jake Bostrom, Robbert Rottier and Christopher Hahn (St. Jude); and Joan Weliky Conaway (Stowers Institute for Medical Research, Kansas City, MO).


St. Jude Children’s Research Hospital

St. Jude Children’s Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, TN, St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fund-raising organization. For more information, please visit www.stjude.org.

Bonnie Cameron | EurekAlert!
Further information:
http://www.stjude.org

More articles from Health and Medicine:

nachricht Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin

nachricht Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

Physicists discover mechanism behind granular capillary effect

24.05.2017 | Physics and Astronomy

Measured for the first time: Direction of light waves changed by quantum effect

24.05.2017 | Physics and Astronomy

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>