Nishimune et al. report.
A neuromuscular junction 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 the muscle, laminin sports α, β, and γ chains and is part of a sheath that covers the muscle fiber. Previous work had shown that the β2 chain of laminin spurs differentiation of the nerve terminal. The team has now found evidence that the α chains of laminin influence post-synaptic patterning. For example, maturation of the post-synaptic side slowed in mice lacking the α5 chain of laminin in their muscles. Moreover, post-synaptic development faltered in myotubes, or muscle fiber precursors, from these mice.
The researchers discovered that laminin corrals molecules of its receptor, dystroglycan, on the post-synaptic surface. Dystroglycan, in turn, gathers receptors that respond to acetylcholine released by the nerve, though how dystroglycan rounds up these receptors is uncertain. Overall, the work suggests that laminin influences pre-synaptic and post-synaptic development, thus providing a way to coordinate maturation of the sending and receiving sides of the synapse.