RT Journal Article
SR Electronic
T1 Neural Agrin Induces Ectopic Postsynaptic Specializations in Innervated Muscle Fibers
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6534
OP 6544
DO 10.1523/JNEUROSCI.17-17-06534.1997
VO 17
IS 17
A1 Thomas Meier
A1 Dominik M. Hauser
A1 Matthias Chiquet
A1 Lukas Landmann
A1 Markus A. Ruegg
A1 Hans R. Brenner
YR 1997
UL http://www.jneurosci.org/content/17/17/6534.abstract
AB 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-β2, MuSK, phosphotyrosine-containing proteins, β-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 aggregationin 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.