Agrin-like molecules at synaptic sites in normal, denervated, and damaged skeletal muscles.
Several lines of evidence have led to the hypothesis that agrin, a protein extracted from the electric organ of Torpedo, is similar to the molecules in the synaptic cleft basal lamina at the neuromuscular junction that direct the formation of acetylcholine receptor and acetylcholinesterase aggregates on regenerating myofibers. One such finding is that monoclonal antibodies against agrin stain molecules concentrated in the synaptic cleft of neuromuscular junctions in rays. In the studies described here we made additional monoclonal antibodies against agrin and used them to extend our knowledge of agrin-like molecules at the neuromuscular junction. We found that anti-agrin antibodies intensely stained the synaptic cleft of frog and chicken as well as that of rays, that denervation of frog muscle resulted in a reduction in staining at the neuromuscular junction, and that the synaptic basal lamina in frog could be stained weeks after degeneration of all cellular components of the neuromuscular junction. We also describe anti-agrin staining in nonjunctional regions of muscle. We conclude the following: (a) agrin-like molecules are likely to be common to all vertebrate neuromuscular junctions; (b) the long-term maintenance of such molecules at the junction is nerve dependent; (c) the molecules are, indeed, a component of the synaptic basal lamina; and (d) they, like the molecules that direct the formation of receptor and esterase aggregates on regenerating myofibers, remain associated with the synaptic basal lamina after muscle damage.
Reist
N E
NE
Department of Neurobiology, Stanford University School of Medicine, California 94305.
Magill
C
C
McMahan
U J
UJ
D018171:Agrin; D000818:Animals; D000911:Antibodies, Monoclonal; D002645:Chickens; D008854:Microscopy, Electron; D009121:Muscle Denervation; D009132:Muscles / Q000032:analysis* / Q000294:innervation / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009469:Neuromuscular Junction / Q000032:analysis* / Q000166:cytology / Q000648:ultrastructure; D011894:Rana pipiens; D051381:Rats; D011919:Rats, Inbred Strains; D012860:Skates, Fish; D013045:Species Specificity; D014101:Torpedo
D018171:Agrin; D000911:Antibodies, Monoclonal; D009419:Nerve Tissue Proteins