| dc.description | Neuregulins: Primary or secondary signals for the
control of synapse-specific gene expression.(Colasante, Cesare.)
Abstract
The selective transcription of acetylcholine receptor (AChR) subunit genes in synaptic myonuclei leads to the accumulation of
AChR subunit mRNAs at the neuromuscular junction (NMJ). This mechanism contributes to the concentration of AChRs at
the postsynaptic sarcolemma, and its physiological significance is underscored by the cases of human congenital myasthenias
caused by mutation in a cis-regulatory element of the AChR£-subunit promoter, which is necessary for its synaptic expression.
The signal(s) that drives synapse-specific expression is unknown but neuregulin-1 (Nrg-1), a group of growth-factor-like
polypeptides encoded by the nrg-1 gene, has been a favorite candidate. Nrg-1 was originally thought as a nerve-derived factor,
acting in parallel to pathways controlling AChR clustering at the synapse (i.e. agrin signaling). However, recent work suggests
that Nrg-1 may actually be a muscle-derived signal that is concentrated at the NMJ, together with its receptors, by agrin and
that acts as a secondary, downstream signal to enhance synapse-specific AChR transcription. Here, I review studies for and
against Nrg-1 as a secondary signal driving synapse-specific expression at the NMJ. In addition, I briefly present new evidence
that raise the possibility that Nrgs encoded by the ngr-1-related gene nrg-2 might have a role controlling AChR expression.
This paper was published on Journal of Neurocytology 32, 665-675 (2003) Section of Neurobiology, Institute for Cell and Molecular Biology, and Institute for Neuroscience, University of Texas at Austin,
Austin, TX 78712, USA | |
