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Mediator in communication between neurons and muscle cells found
Date:10/22/2008

A missing piece of the puzzle of how neurons and muscle cells establish lifelong communication has been found by researchers who suspect this piece may be mutated and/or attacked in muscular dystrophy.

Agrin is a protein that motor neurons release to direct construction of the nerve-muscle contact or synapse. MuSK on the muscle cell surface initiates critical internal cell talk so synpases can form and receptors that enable specific commands will cluster at just the right spot.

The conundrum was agrin and MuSK don't directly communicate, explains Dr. Lin Mei, chief of developmental neurobiology at the Medical College of Georgia and Georgia Research Alliance Eminent Scholar in Neuroscience.

Much as a friend gets two other friends together, MCG researchers have found that agrin starts talking with LRP4, a protein also on the muscle cell surface, then recruits MuSK to join the conversation. LRP4 and MuSK become major components of the receptor needed for the muscle cell to receive the message agrin is sending, says Dr. Bin Zhang, postdoctoral fellow in Dr. Mei's lab and first author on the paper published in the Oct. 23 issue of the journal Neuron.

"We know agrin is important and we know MuSK is important. The puzzle or greatest gap in this field for a long time is there was no evidence these two would shake hands but they must have each other," says Dr. Mei, corresponding author. "This paper shows that this protein, LRP4, forms a nice bridge between the two and solves this long puzzle."

The agrin-MuSK signaling pathway has been implicated in muscular dystrophy, a group of genetic diseases that lead to loss of muscle control because of problems with neurons, muscle cells and/or their communication. Some reports have implicated a mutant MuSK as a cause of muscular dystrophy and autoantibodies (antibodies the body makes against itself) to MuSK have been found in the blood of some patients.

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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
Source:Eurekalert  

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