The Journal of Neuroscience, June 1, 1998, 18(11):4166-4176
Rapsyn Clusters Neuronal Acetylcholine Receptors But Is
Inessential for Formation of an Interneuronal Cholinergic Synapse
Guoping
Feng1,
Joe
Henry
Steinbach2, and
Joshua R.
Sanes1
Departments of 1 Anatomy and Neurobiology and
2 Anesthesiology, Washington University School of
Medicine, St. Louis, Missouri 63110
Nicotinic acetylcholine receptors (AChRs) are clustered at high
density in the postsynaptic membranes of skeletal neuromuscular junctions and cholinergic interneuronal synapses. A cytoplasmic protein, rapsyn, is essential for AChR clustering in muscle. Here, we
asked whether rapsyn mediates neuronal AChR clustering at cholinergic synapses in a mammalian sympathetic ganglion, the superior cervical ganglion (SCG). Several observations supported this possibility: (1)
AChR clusters containing the 
3-5 and 
2 subunits, homologs of the
muscle AChR subunits, are present at SCG synapses; (2) rapsyn RNA is
readily detectable in the SCG; and (3) expression of recombinant rapsyn
in heterologous cells induces aggregation of coexpressed neuronal AChR
subunits. However, rapsyn protein was undetectable at ganglionic
synaptic sites. Moreover, aggregates of neuronal AChRs induced in
heterologous cells by full-length rapsyn remained intracellular,
whereas rapsyn-induced clusters of muscle AChRs reached the cell
surface. Additional studies revealed a second rapsyn RNA species in SCG
generated by alternative splicing and competent to encode a novel short
rapsyn isoform. However, this isoform clustered neither neuronal nor
muscle AChRs in heterologous cells. Most telling, the number, size, and
density of AChR clusters in SCG did not differ significantly between
neonatal mice bearing a targeted mutation of the rapsyn gene and
littermate controls. Thus, rapsyn is dispensable for clustering of
ganglionic neuronal nicotinic AChRs.
Key words:
acetylcholine receptor; knock-out; mouse; postsynaptic; rapsyn; superior cervical ganglion; synaptogenesis
Copyright © 1998 Society for Neuroscience 0270-6474/98/18114166-11$05.00/0
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