Laminin Builds The Neuromuscular Synapse

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Laminin Builds The Neuromuscular Synapse

http://medicalnewscenter.com/out/out.cgi?

http://www.sciencedaily.com/releases/2008/09/080915083339.htm

Like a plug and a socket, a nerve and a muscle fiber mesh at the

neuromuscular junction. New work reveals that an extracellular matrix

protein called laminin shapes both sides of the junction to ensure

they fit together.

A neuromuscular junction, or synapse, in a newborn mouse is

functional but simple, with a globular nerve terminal meeting a flat,

oval structure on the muscle fiber. As the animal matures, the nerve

terminal branches into a claw shape, and the muscle side contorts

into a matching conformation. But what coordinates these changes so

the two sides mirror each other? The researchers think that one

molecule in the synapse sculpts both sides.

Their chief suspect was the synapse-spanning protein laminin. Made by

muscle and forming part of the sheath that covers muscle, the laminin

protein has different domains called alpha, beta, and gamma chains.

Previous work had shown that the beta2 chain of laminin spurs

differentiation of the nerve terminal. The team has now found

evidence that the alpha chains of laminin influence post-synaptic

patterning. For example, maturation of the muscle side slowed in mice

lacking the alpha5 chain of laminin in their muscles.

The researchers discovered that cell surface receptor molecules that

recognize and bind laminin, are corralled by laminin on the muscle

side of the synapse. These receptors, in turn, gather other receptors

that respond to signals from the nerve. Overall, the work suggests

that the beta and alpha chains of laminin together influence pre-

synaptic and post-synaptic development, thus providing a way to

coordinate maturation of the sending and receiving sides of the

synapse.

Journal reference:

Nishimune, H., et al. . Journal of Cell Biology, (in press) DOI:

10.1083/jcb.200805095