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: Putting the squeeze on a cell's nucleus

Related Stories

Putting the squeeze on a cell's nucleus

June 16, 2015

Nuclear membranes protect genes—life's most precious cargo—but little is known about why they function in different tissue types. For instance, nuclei in brain cells tend to be soft and pliable while those in bone cells ...

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 ...

Blueprints for the construction of nuclear pores deciphered

May 6, 2015

In a recent study, a team of researchers led by Alwin Köhler at the Max F. Perutz Laboratories (MFPL) belonging to the University of Vienna and the Medical University of Vienna offer new insights into how nuclear pores are ...

Recommended for you

Male seahorse and human pregnancies remarkably alike

September 1, 2015

Their pregnancies are carried by the males but, when it comes to breeding, seahorses have more in common with humans than previously thought, new research from the University of Sydney reveals.

Parasitized bees are self-medicating in the wild, study finds

September 1, 2015

Bumblebees infected with a common intestinal parasite are drawn to flowers whose nectar and pollen have a medicinal effect, a Dartmouth-led study shows. The findings suggest that plant chemistry could help combat the decline ...

How wind sculpted Earth's largest dust deposit

September 1, 2015

China's Loess Plateau was formed by wind alternately depositing dust or removing dust over the last 2.6 million years, according to a new report from University of Arizona geoscientists.

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.