Willis et al. Unique sets of mRNAs, the findings show, are brought to or warded off from axon sites in contact with neuronal growth factors.
Axons have their own translational machinery that allows them to respond to stimuli rapidly. Stores of transcripts lie in wait near axonal ribosomes, ready to be translated when called upon. The make-up of these stores, the new results reveal, can be changed locally by extracellular cues.
To measure store changes, the group first took an inventory of messages that are translated in injured axons, which ramp up local protein synthesis. Using this baseline, the authors then calculated transcript changes at sites also exposed to extracellular growth factors.
Growth-promoting neurotrophins caused some nearby transcript levels to increase and others to decrease. Growth inhibitors such as myelin-associated glycoprotein often had the opposite effects on those same transcripts.
Not all mRNAs were affected equally by growth promoters. The GAP43 transcript was attracted by NGF but not BDNF. And the necessary signaling pathways also differed. Trk neurotrophin receptors were commonly required, but only some transcript changes also required either or both PI3K and MAP kinase signaling.
The attraction of messages by neurotrophins required transport along microtubules both back to the cell body and out to the axon. This messaging system probably tells the cell body to send out the necessary new recruits. Indeed, levels of specific transcripts in the cell body dropped as they increased in the axon.
Changes in transcripts that were repulsed by growth inhibitors did not require microtubule transport back to the body. These axonal transcripts might be either degraded, sent further out into the axon, or transported along actin instead.
In addition to neurons, fibroblasts and muscle cells also locally translate specific messages. Although isolating small areas of their cytoplasm would be difficult, these and other cell types probably also change transcript stores in response to extracellular cues.