PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

A trigger for muscular diseases

2014-01-27
(Press-News.org) Contact information: Rita Sullivan King
news@rupress.org
212-327-8603
Rockefeller University Press
A trigger for muscular diseases

Various muscular diseases are associated with changes in the elasticity of the protein titin, but whether these changes are a cause or an effect of disease has been unclear. A study in The Journal of General Physiology helps solve this "chicken or the egg" conundrum and identifies a key player in determining titin's size and stiffness.

Titin is an enormous protein that functions as a molecular spring responsible for the passive elasticity of muscles. It is composed of many individually folded protein domains—including repeating immunoglobulin-like (Ig) domains—that unfold when the protein is stretched and refold when tension is removed.

A team led by researchers from the University of Arizona used a mouse model lacking nine titin Ig domains to investigate the effects of a small increase in titin stiffness. The mutant mice showed a slight curvature of the spine (commonly associated with skeletal muscle disorders), atrophy of the soleus muscle in the leg, atrophy of the diaphragm, and changes in muscle contractility.

In analyzing the mutant mice, the researcher were surprised to observe that in the soleus, which contains one of the largest forms of titin in adult striated muscle, the increase in passive stress was much greater than expected from the loss of only nine Ig domains. And the mutant mice underwent additional changes in titin splicing to produce much smaller, stiffer forms of titin than anticipated. These results indicate that increasing titin's stiffness can be a trigger for—rather than the result of—pathological changes in skeletal muscles.

Further investigation revealed that titin's increased stiffness was caused by an abundance of the splicing factor RBM20 in the mutant mice. Mice created by crossing the mutants with a mouse with decreased RMB20 activity failed to show these additional changes in titin splicing. The results indicate that RMB20 plays a crucial role in determining titin's size and elasticity and could therefore be a possible avenue for modulating the protein in the treatment of various muscular diseases.



INFORMATION:

Buck, D., et al. 2014. J. Gen. Physiol. doi:10.1085/jgp.201311129

About The Journal of General Physiology

Founded in 1918, The Journal of General Physiology (JGP) is published by The Rockefeller University Press. All editorial decisions on manuscripts submitted are made by active scientists in conjunction with our in-house scientific editor. JGP content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works and third parties may reuse the content for non-commercial purposes under a creative commons license. For more information, please visit http://www.jgp.org.

Research reported in the press release was supported by the Bellows Foundation, the ARCS Foundation, the American Heart Association, and the National Institutes of Health.



ELSE PRESS RELEASES FROM THIS DATE:

Unexpected player in regulation of blood cholesterol levels

2014-01-27
Kinesins are motor proteins that "walk" along microtubules and transport various cargoes throughout the cell. A study in The Journal of Cell Biology uncovers an unexpected role for one kinesin in ...

Protecting the skin from sun exposure

2014-01-27
The ultraviolet radiation (UVR) present in sunlight is the most common environmental carcinogen, and long-term exposure to UVR can lead to skin cancer and premature aging of the skin. To develop better methods of ...

HRT therapy may increase risk of acute pancreatitis

2014-01-27
Women who use postmenopausal hormone replacement therapy (HRT) may be at increased risk of acute pancreatitis, found a new study in CMAJ (Canadian Medical Association Journal). Acute pancreatitis, ...

Preventing and treating the common cold: Nothing to sneeze at

2014-01-27
How do you prevent and treat the common cold? Handwashing and zinc may be best for prevention whereas acetaminophen, ibuprofen and perhaps ...

The science of baby-making still a mystery for many women

2014-01-27
A new study by Yale School of Medicine researchers provides insight into how much women of reproductive age in the United States know about reproductive health. Published in the Jan. 27 issue of Fertility & Sterility, ...

Cannabis during pregnancy endangers fetal brain development

2014-01-27
An increasing number of children suffer from the consequences of maternal drug exposure during pregnancy, and Cannabis is one of the most frequently used substances. This motivated the study, published in ...

New method increases supply of embryonic stem cells

2014-01-27
A new method allows for large-scale generation of human embryonic stem cells of high clinical quality. It also allows for production of such cells without destroying any human embryos. The discovery is a big step forward ...

Cracks in the cellular transport system can be key to a new generation of cancer therapies

2014-01-27
Researchers from Warwick Medical School have discovered a critical point of failure in the microscopic transport system that operates inside every cell in the human body. The ...

Ottawa researchers discover new combination therapy to kill cancer

2014-01-27
OTTAWA, ON – January 27, 2014 – Cancer is the leading cause of death in Canada and is responsible for about 30% of all deaths, according to the Canadian ...

Study on DSM-5 shows effects on autism diagnosis and prevalence

2014-01-27
NEW YORK, N.Y. (January 27, 2014)— A new study finds that ...

LAST 30 PRESS RELEASES:

Robotic space rovers keep getting stuck. UW engineers have figured out why

New research shows how immigration status can become a death sentence during public health crisis

University of Toronto Engineering researchers develop safer alternative non-stick coating

Good vibrations: Scientists use imaging technology to visualize heat

More ecological diversity means better nutritional resources in Fiji’s agroforests

New global study shows freshwater is disappearing at alarming rates

Scientists create an artificial cell capable of navigating its environment using chemistry alone

A little salt is good for battery health

Deep-sea fish confirmed as a significant source of ocean carbonate

How to keep kids with eating disorders home after hospital stay? Therapy

Sex differences affect efficacy of opioid overdose treatment

Aligning AI with Human Values and Well-Being

Engineering the next generation of experimental physics

The scuba diving industry is funding marine ecosystem conservation and employing locals

BATMAN brings TCR therapy out of the shadows

Surrogates more likely to be diagnosed with mental illness, study finds

Columbia Engineering researchers turn dairy byproduct into tissue repair gel

Global estimates of lives and life-years saved by COVID-19 vaccination during 2020-2024

Potential trade-offs of proposed cuts to the NIH

New research simulates cancer cell behavior

COVID, over 2.5 million deaths prevented worldwide thanks to vaccines. One life saved for every 5,400 doses administered

Scuba diving generates up to $20 billion annually

Scientists advance efforts to create ‘virtual cell lab’ as testing ground for future research with live cells

How DNA packaging controls the “genome’s guardian”

Simplified models, deeper insights: Coarse-grained models unlock new potential for ionic liquid simulations

Gorillas’ personal circumstances shape their aggression towards groupmates

Which signalling pathways in the cell lead to possible therapies for Parkinson's disease

Identifying landslide threats using hydrological predictors

First graders who use more educational media spend more time reading

Exploring the meaning in life through phenomenology and philosophy

[Press-News.org] A trigger for muscular diseases