Featured Research

from universities, journals, and other organizations

Researchers find culprit behind skeletal muscle disease

Date:
January 28, 2014
Source:
University of Arizona
Summary:
Genetic mutations in titin, a protein that is vital for proper muscular function, can cause skeletal muscle disease, according to a new study. The work answers a question that remained after previous studies, which couldn't say if the deviations caused myopathies, or merely resulted from them.

Danielle Buck's study is the first to show that mutations to the titin gene cause skeletal muscle myopathies, and could pave the way to finding a cure for muscular disease.
Credit: Beatriz Verdugo/UANews

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.

Related Articles


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.


Story Source:

The above story is based on materials provided by University of Arizona. The original article was written by Shelley Littin. Note: Materials may be edited for content and length.


Journal Reference:

  1. D. Buck, J. E. Smith, C. S. Chung, Y. Ono, H. Sorimachi, S. Labeit, H. L. Granzier. Removal of immunoglobulin-like domains from titin's spring segment alters titin splicing in mouse skeletal muscle and causes myopathy. The Journal of General Physiology, 2014; 143 (2): 215 DOI: 10.1085/jgp.201311129

Cite This Page:

University of Arizona. "Researchers find culprit behind skeletal muscle disease." ScienceDaily. ScienceDaily, 28 January 2014. <www.sciencedaily.com/releases/2014/01/140128130507.htm>.
University of Arizona. (2014, January 28). Researchers find culprit behind skeletal muscle disease. ScienceDaily. Retrieved October 31, 2014 from www.sciencedaily.com/releases/2014/01/140128130507.htm
University of Arizona. "Researchers find culprit behind skeletal muscle disease." ScienceDaily. www.sciencedaily.com/releases/2014/01/140128130507.htm (accessed October 31, 2014).

Share This



More Health & Medicine News

Friday, October 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Melafind: Spotting Melanoma Without a Biopsy

Melafind: Spotting Melanoma Without a Biopsy

Ivanhoe (Oct. 31, 2014) The MelaFind device is a pain-free way to check suspicious moles for melanoma, without the need for a biopsy. Video provided by Ivanhoe
Powered by NewsLook.com
Battling Multiple Myeloma

Battling Multiple Myeloma

Ivanhoe (Oct. 31, 2014) The answer isn’t always found in new drugs – repurposing an ‘old’ drug that could mean better multiple myeloma treatment, and hope. Video provided by Ivanhoe
Powered by NewsLook.com
Chronic Inflammation and Prostate Cancer

Chronic Inflammation and Prostate Cancer

Ivanhoe (Oct. 31, 2014) New information that is linking chronic inflammation in the prostate and prostate cancer, which may help doctors and patients prevent cancer in the future. Video provided by Ivanhoe
Powered by NewsLook.com
Sickle Cell: Stopping Kids’ Silent Strokes

Sickle Cell: Stopping Kids’ Silent Strokes

Ivanhoe (Oct. 31, 2014) Blood transfusions are proving crucial to young sickle cell patients by helping prevent strokes, even when there is no outward sign of brain injury. Video provided by Ivanhoe
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins