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.
Department of Neurobiology, Stanford University School of Medicine, Stanford, California, 94305, USA.
M
M
Rimer
I
I
Cohen
T
T
Lømo
S J
SJ
Burden
U J
UJ
McMahan
D018171:Agrin / Q000502:physiology*; D000818:Animals; D018076:DNA, Complementary; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000502:physiology; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics*; D008297:Male; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000294:innervation / Q000502:physiology; D020880:Neuregulins; D009469:Neuromuscular Junction / Q000737:chemistry* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020893:Receptor, ErbB-3; D013569:Synapses / Q000737:chemistry / Q000502:physiology; D014162:Transfection
D018171:Agrin; D018076:DNA, Complementary; D006023:Glycoproteins; D020880:Neuregulins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D066246:ErbB Receptors; D020893:Receptor, ErbB-3