Lamin A/C deficiency is 'unnerving'

Jan 05, 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: Sex? It all started 385 million years ago (w/ Video)

add to favorites email to friend print save as pdf

Related Stories

Air Umbrella R&D evolves as shield from pelting rain

24 minutes ago

A Chinese R&D team have invented an Air Umbrella which can blast water away from the umbrella's owner. They explain how their invention deflects rain: "Air is everywhere on the earth. The flowing air can ...

Weather history time machine

34 minutes ago

During the 1930s, North America endured the Dust Bowl, a prolonged era of dryness that withered crops and dramatically altered where the population settled. Land-based precipitation records from the years ...

Light pollution contributing to fledgling 'fallout'

54 minutes ago

Turning the street lights off decreased the number of grounded fledglings, according to a study published October 15, 2014 in the open-access journal PLOS ONE by Airam Rodríguez and colleagues from Phillip Island Nature ...

Recommended for you

Scientists see how plants optimize their repair

1 hour ago

Researchers led by a Washington State University biologist have found the optimal mechanism by which plants heal the botanical equivalent of a bad sunburn. Their work, published in the Proceedings of the Na ...

User comments : 0