Lamin A/C deficiency is 'unnerving'

January 5, 2009,
Lmna -/- animals have disorganized neuromuscular synapses (green) without postsynaptic nuclei (blue). Credit: Méjat, A., et al. 2008. J. Cell Biol.

Mutations in the nuclear intermediate filament lamin A/C (LMNA) gene are associated with Emery-Dreifuss muscular dystrophy, but cause the disease by unknown mechanisms. Méjat et al. show that one mechanism involves the disruption of neuromuscular junctions.

The study will appear online on Monday, January 5, 2009 (www.jcb.org) and in the January 12, 2009 print issue of the Journal of Cell Biology.

Muscle fiber cells contain hundreds of nuclei. In normal fibers, several nuclei cluster together under the cell membrane at sites of neuronal contact. These postsynaptic nuclei synthesize the components of the neuromuscular junction that specify the overlying membrane as the target site for innervation. The authors found that LMNA-deficient animals (including those with a point mutation in LMNA that in humans can cause Emery-Dreifuss disease) failed to position nuclei into these postsynaptic clusters. This prevented the proper organization of the neuromuscular junction and disrupted muscle fiber innervation, says author Alexandre Méjat.

The authors showed that either loss or mutation of LMNA disrupted nuclear positioning by causing the mislocalization of two other proteins: Nesprin-1, which spans the outer nuclear membrane and anchors nuclei to the actin cytoskeleton, and SUN2, which spans the inner nuclear membrane, linking Nesprin to lamin A/C. Although lamin A/C is ubiquitously expressed, LMNA defects specifically affected striated and skeletal muscle because Nesprin-1 and SUN2 are highly expressed in these tissues. Samples from Emery-Dreifuss muscular dystrophy patients exhibit similar hallmarks of skeletal muscle functional denervation, suggesting the authors are on the right track.

Paper: Méjat, A., et al. 2008. J. Cell Biol. doi:10.1083/jcb.200811035.

Source: Rockefeller University

Explore further: Alzheimer's-associated tau protein disrupts molecular transport within neurons

Related Stories

Organizing a cell's genetic material from the sidelines

June 28, 2018

A tremendous amount of genetic material must be packed into the nucleus of every cell—a tiny compartment. One of the biggest challenges in biology is to understand how certain regions of this highly packaged DNA can be ...

New technique enables study of 'challenging' proteins

November 14, 2011

Researchers from Hull, Bristol and Frankfurt have shown that a new technique for identifying molecular structure can be used effectively on small samples of biological proteins, particularly proteins that are targeted for ...

Nano-Probes Allow an Inside Look at Cell Nuclei

March 18, 2005

Nanotechnology may be in its infancy, but biologists may soon use it to watch the inner workings of a living cell like never before. Scientists at the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley ...

Recommended for you

First to red planet will become Martians: Canada astronaut

September 22, 2018

Astronauts traveling through space on the long trip to Mars will not have the usual backup from mission control on Earth and will need to think of themselves as Martians to survive, Canada's most famous spaceman half-jokingly ...

New battery gobbles up carbon dioxide

September 21, 2018

A new type of battery developed by researchers at MIT could be made partly from carbon dioxide captured from power plants. Rather than attempting to convert carbon dioxide to specialized chemicals using metal catalysts, which ...

Ocean acidification may reduce sea scallop fisheries

September 21, 2018

Each year, fishermen harvest more than $500 million worth of Atlantic sea scallops from the waters off the east coast of the United States. A new model created by scientists at the Woods Hole Oceanographic Institution (WHOI), ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.