Neuregulins and erbB Receptors at Neuromuscular Junctions and at Agrin-Induced Postsynaptic-like Apparatus in Skeletal Muscle

We demonstrate by immunohistochemistry that at least two isoforms of neuregulin (NRG) are concentrated at neuromuscular junctions in adult rat muscles. One is NRGbeta3, a secreted protein which is bound to basal lamina that occupies the synaptic cleft. The other(s), NRG-a, is in the muscle fibers' plasma membrane. We show further that muscle NRG, including NRG-a, is concentrated at postsynaptic-like apparatus induced to form in the extrajunctional region of the soleus muscle by exposure to neural agrin. The agrin-induced postsynaptic-like apparatus also includes aggregates of the NRG receptors erbB2 and erbB3 as does postsynaptic apparatus at neuromuscular junctions. These findings together with those of others suggest a mechanism by which neural agrin induces the expression of epsilon-AChR subunits in postsynaptic-like apparatus, and they support the hypothesis that agrin has a similar function at neuromuscular junctions.