Nov. 5, 2008

Missing Link ID'd At Nerve-Muscle Junction

MDA grantee Lin Mei recently coordinated a team of scientists who identified a previously missing link necessary to the mechanism that allows signals to pass from nerve to muscle cells. Without these signals, muscles cannot contract.

The protein, known as LRP4, is now known to connect two other proteins, agrin and MuSK, at the neuromuscular junction, the meeting place of nerve and muscle fibers.

"LRP4 is both necessary and sufficient to bind [stick] to agrin and activate MuSK signaling," note Bin Zhang at the Medical College of Georgia and colleagues, who published their findings in the Oct. 23 issue of the journal Neuron. The MuSK protein tells the part of the muscle fiber that receives nerve signals to form and maintain clusters of special landing pads for these signals.

Mei also notes that another research group, led by Steven Burden at New York University in Manhattan, independently made the same discovery and published it Oct. 17 in the journal Cell.

Disruptions of signal transmission at the neuromuscular junction can be caused by a mistaken immune-system attack on any of several of its components or by genetic abnormalities in these components.

Immune-system destruction of the signaling protein MuSK or the landing pads, which are called acetylcholine receptors, cause myasthenia gravis (MG), a disease involving interrupted signals that lead to fluctuating weakness.

The investigators note that their results "suggest that LRP4 may be a potential culprit" as well in this type of disorder and could become a new target for therapies.