Neuron-wide RNA transport combines with netrin-mediated local translation to spatially regulate the synaptic proteome

The nervous system contains billions of cells called neurons that connect to each other to form complex networks via junctions known as synapses. Synapses form between the end of an elongated section (called the axon) of one neuron and the tiny projections (or dendrites) from the cell body of the next neuron. Throughout the lifespan of an animal, the nervous system responds to experiences and stimuli from the environment by changing the strength of the connections at synapses; this is known as ‘synaptic plasticity’. In this way, long-term information about learning and memory can be stored and used to direct future responses to similar situations. Many proteins are involved in forming and altering synapses. The genes that code for these proteins are found in the nucleus of the neuron within the cell body. To make new proteins, copies of genes are made using molecules called mRNAs, which then leave the nucleus and are used as templates by the machinery that assemble proteins. Previous studies have shown that mRNA molecules are transported from the cell body to the axon and dendrites, but it is not clear exactly where the proteins are produced. Kim et al. have now studied the movement of mRNAs in neurons from the sea slug Aplysia during synapse formation and synapse plasticity. This showed that mRNAs are delivered equally throughout the neuron, and so it appears that mRNAs are not targeted to a particular synapse. However, the level of protein production using these mRNA molecules is much higher in places where synapses are being formed or altered. A protein called netrin-1 promotes protein production in the dendrites of neurons at these synapses. Kim et al. demonstrate that although mRNAs are delivered throughout the neuron, they are only used to make proteins at specific synapses. This allows the entire neuron to be in a state of readiness to make new synapses or alter existing ones in response to stimuli from the environment. Understanding more about how this local control of protein production works within neurons may provide new insights into diseases that affect synaptic plasticity.