Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


UA Researchers Find Culprit Behind Skeletal Muscle Disease

A University of Arizona doctoral candidate has shown for the first time that genetic mutations in the titin gene can cause skeletal muscle myopathy, a disease in which muscle fibers do not function properly, resulting in muscle weakness. Myopathic disease can affect heart muscles as well as skeletal muscles, and titin is responsible for many problems associated with heart disease.

The research was done by Danielle Buck, a doctoral candidate in the UA’s Department of Molecular and Cellular Biology. She worked under the direction of Henk Granzier, a professor in cellular and molecular medicine and physiology, who has studied titin for years.

Previous studies had shown that alterations in titin are involved in muscular myopathies, but whether these deviations actually cause myopathies, or merely result from them, has remained a mystery.

Buck has shown that mutations in the titin gene do in fact cause myopathies in skeletal muscles. Her study, published today in the Journal of General Physiology, could be an important first step in developing treatments to address causes of the disease.

“Patients with muscle myopathy experience muscle weakness, but not a lot has been known about what is going wrong at the molecular and genetic level, except that titin is often involved,” Buck said. “Many patients with heart disease also have mutations in titin. So to develop treatments we need to understand the structure of titin and how it can cause or respond to disease.”

“With about 35,000 amino acids, titin is the largest protein known, roughly 100 times larger than typical proteins, which have only around several hundred amino acids,” Granzier explained. Amino acids are the building blocks of proteins.

Titin, he said, functions as a molecular spring that makes tissues elastic so that when they deform they can snap back again. “Titin is a vital determinant of the elasticity of skeletal and heart muscles, which is very important for normal muscular function,” he noted.

“Titin is like the stretchy material in a rubber balloon,” said Buck. “If you have a balloon that is too stretchy or too stiff, then it’s not going to be able to expand or contract. Tissues also need to have elasticity so that they can restore their original shape after they have been contracted.”

Conducting genetic testing for mutations in the titin gene and studying the defects in the protein have been challenging due to titin’s “enormous size,” Granzier said. “But excellent facilities at the University of Arizona have enabled researchers to make great impact and progress has recently accelerated.”

Buck’s research “has directly shown that introducing specific changes to the titin gene can lead to disease in skeletal muscles,” Granzier said. “We know now that titin itself can trigger the disease. Danielle’s research shows that this giant protein needs to be tuned just right or it can cause myopathies to develop in skeletal muscles.”

Buck’s research “also demonstrated for the first time that changing a part of the gene results in a cascade of additional damaging changes in the protein,” he added.

“We found that in skeletal muscles, deleting one area of titin can affect expression of the entire protein and other areas can subsequently be deleted as well,” Buck said. “Shortening titin leads to a cascade of effects that cause titin to be even shorter, and that causes the muscle to become very stiff.”

Buck approached her work from many levels, Granzier said. “She worked at the gene level, the transcription level, the protein level and the functional level of cells and tissues to get an integrative understanding of the changes that this genetic modification caused.”

“We try to look at all these levels so that we can get a deeper understanding of the mechanisms that give rise to disease,” he added. “It is a multidisciplinary study, from molecular and cellular biology to integrative physiology.”

Understanding what factors cause myopathies could enable researchers to reverse the disease in humans by developing medications to counter damaging activity of the gene, Buck said.

“The next step ideally would be to use this model as an avenue to find new future therapeutic targets,” she said.

Buck already has begun to forge into research around a possible cure for myopathies.

Granzier’s lab, including John Smith and Charles Chung, collaborated with researchers at the Tokyo Metropolitan Institute of Medical Science in Japan and at the University of Heidelberg in Germany. The study was supported by National Institutes of Health grants to Granzier as well as fellowships from the Bellows Foundation and the ARCS Foundation to Buck.

This story and photos are online:

Research paper:


Henk Granzier
Professor, Molecular and Cellular Biology and Physiology
Danielle Buck
Doctoral candidate, Molecular and Cellular Biology
UANews Contact
Shelley Littin

Shelley Littin | UANews
Further information:

More articles from Health and Medicine:

nachricht Older patients recover more slowly from concussion
06.10.2015 | Radiological Society of North America

nachricht Fatty liver disease and scarring have strong genetic component
02.10.2015 | University of California - San Diego

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: Physicists shrink particle accelerator

Prototype demonstrates feasibility of building terahertz accelerators

An interdisciplinary team of researchers has built the first prototype of a miniature particle accelerator that uses terahertz radiation instead of radio...

Im Focus: Simple detection of magnetic skyrmions

New physical effect: researchers discover a change of electrical resistance in magnetic whirls

At present, tiny magnetic whirls – so called skyrmions – are discussed as promising candidates for bits in future robust and compact data storage devices. At...

Im Focus: High-speed march through a layer of graphene

In cooperation with the Center for Nano-Optics of Georgia State University in Atlanta (USA), scientists of the Laboratory for Attosecond Physics of the Max Planck Institute of Quantum Optics and the Ludwig-Maximilians-Universität have made simulations of the processes that happen when a layer of carbon atoms is irradiated with strong laser light.

Electrons hit by strong laser pulses change their location on ultrashort timescales, i.e. within a couple of attoseconds (1 as = 10 to the minus 18 sec). In...

Im Focus: Battery Production: Laser Light instead of Oven-Drying and Vacuum Technology

At the exhibition BATTERY + STORAGE as part of WORLD OF ENERGY SOLUTIONS 2015 in Stuttgart, the Fraunhofer Institutes for Laser Technology ILT and for Ceramic Technologies and Systems IKTS will be showing how laser technology can be used to manufacture batteries both cost- and energy-efficiently.

In the truest sense, it’s all about watts at the Dresden-based Fraunhofer Institute for Ceramic Technologies and Systems IKTS and the Aachen-based Fraunhofer...

Im Focus: New Sinumerik features improve productivity and precision

EMO 2015, Hall 3, Booth E06/F03

  • Drive optimization called automatically by the part program boosts productivity
  • Automatically switching the dynamic values to rapid traverse and interpolation...
All Focus news of the innovation-report >>>



Event News

EHFG 2015: Securing healthcare and sustainably strengthening healthcare systems

01.10.2015 | Event News

Conference in Brussels: Tracking and Tracing the Smallest Marine Life Forms

30.09.2015 | Event News

World Alzheimer`s Day – Professor Willnow: Clearer Insights into the Development of the Disease

17.09.2015 | Event News

Latest News

Graphene teams up with two-dimensional crystals for faster data communications

06.10.2015 | Information Technology

Laser-wielding physicists seize control of atoms' behavior

06.10.2015 | Physics and Astronomy

Flipping molecular attachments amps up activity of CO2 catalyst

06.10.2015 | Life Sciences

More VideoLinks >>>