Neuregulins at the neuromuscular synapse: past, present, and future

At the developing vertebrate neuromuscular junction, neuregulins are growth/differentiation factors essential for terminal Schwann cell survival. Neuregulins have also been thought as the critical signals responsible for the increased transcription of acetylcholine receptor subunit genes at the neuromuscular synapse. This latter role is now highly controversial. This article reviews the evidence that has shaped the views of the neuregulins and how these views have been challenged. The most recent experiments indicate that neuregulin signaling to postsynaptic muscle fibers may modulate, rather than determine, acetylcholine receptor expression at the neuromuscular junction. Based on findings from my lab and those of others, I propose that this modulation might involve novel posttranscriptional molecular mechanisms. Finally, I also suggest that neuregulin signaling may have an important role to play in mediating the response of adult terminal Schwann cells to denervation.