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Volume 17, Number 17,
Issue of September 1, 1997
pp. 6534-6544
Copyright ©1997 Society for Neuroscience
Neural Agrin Induces Ectopic Postsynaptic Specializations in
Innervated Muscle Fibers
Received April 29, 1997; revised June 9, 1997; accepted June 11, 1997.
Thomas Meier1,
Dominik
M. Hauser3,
Matthias Chiquet4,
Lukas Landmann2,
Markus A. Ruegg3, and
Hans R. Brenner1
Institutes of 1 Physiology and 2 Anatomy
and 3 Biozentrum, University of Basel, CH-4051 Basel,
Switzerland, and 4 Maurice E. Müller Institute for
Biomechanics, University of Berne, CH-3010 Berne, Switzerland
Neural agrin, in the absence of a nerve terminal, can induce the
activity-resistant expression of acetylcholine receptor (AChR) subunit
genes and the clustering of synapse-specific adult-type AChR channels
in nonsynaptic regions of adult skeletal muscle fibers. Here we show
that, when expression plasmids for neural agrin are injected into the
extrasynaptic region of innervated muscle fibers, the following
components of the postsynaptic apparatus are aggregated and colocalized
with ectopic agrin-induced AChR clusters: laminin- 2, MuSK,
phosphotyrosine-containing proteins, -dystroglycan, utrophin, and
rapsyn. These components have been implicated to play a role in the
differentiation of neuromuscular junctions. Furthermore, ErbB2 and
ErbB3, which are thought to be involved in the regulation of neurally
induced AChR subunit gene expression, were colocalized with
agrin-induced AChR aggregates at ectopic nerve-free sites. The
postsynaptic muscle membrane also contained a high concentration of
voltage-gated Na+ channels as well as deep, basal
lamina-containing invaginations comparable to the secondary synaptic
folds of normal endplates. The ability to induce AChR aggregation
in vivo was not observed in experiments with a
muscle-specific agrin isoform. Thus, a motor neuron-specific agrin
isoform is sufficient to induce a full ectopic postsynaptic apparatus
in muscle fibers kept electrically active at their original endplate
sites.
Key words:
neuromuscular junction;
MuSK;
utrophin;
rapsyn;
laminin-2;
agrin -dystroglycan;
ErbB receptor;
acetylcholine
receptor;
sodium channel
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