Much as a plug fits its socket, the two sides of the neuromuscular junction are complementary. Nahm et al. show that the same protein shapes both sides of this synapse, helping ensure a good match.
Development of the neuromuscular junction is interactive. The postsynaptic side releases a protein called Glass bottom boat (Gbb) that spurs the neuron to grow toward the muscle. A pathway that includes Cdc42 curbs release of Gbb. Previous work suggested that the protein Rich-1 inactivates Cdc42 in other systems, but researchers didn't know whether Rich-1 affected synapse development.
By screening mutants, Nahm et al. found that the fruit fly equivalent of Rich-1, dRich, alters synapse architecture. Flies lacking the protein showed several presynaptic defects. They carried fewer synaptic boutons, for example, and released less neurotransmitter.
The other side of the junction was also flawed in dRich-deficient insects. The subsynaptic reticulum, a network of membranous tubes beneath the postsynaptic membrane, was misshapen. Some subunits of the glutamate receptors that receive synaptic signals were in the wrong location, failing to cluster opposite active zones, the neurotransmitter launching points on the presynaptic terminal. Overall, losing dRich impaired the neuromuscular junction so that stimulating the neuron induced a 50% smaller current than in controls.
The researchers think that dRich exerts it effects on the presynaptic side by blocking postsynaptic Cdc42 and unleashing Gbb. On the postsynaptic side, the protein might alter membrane folding or bring in helpers that renovate the junction.
