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Journal of Neuroscience, Vol 9, 1294-1302, Copyright © 1989 by Society for Neuroscience
Agrin-induced specializations contain cytoplasmic, membrane, and extracellular matrix-associated components of the postsynaptic apparatus
BG Wallace
Department of Neurobiology, Stanford University School of Medicine, California 94305.
The aims of the studies reported here were to determine the extent to which
the specializations induced by agrin on cultured chick myotubes resemble
the postsynaptic apparatus and examine how these specializations form. We
found that agrin induces the formation of specializations at which at least
6 components of the postsynaptic apparatus are concentrated: one
cytoplasmic component [a 43 kDa acetylcholine receptor (AChR)-associated
protein], 3 membrane components [AChRs and globular forms of
acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)], and 2
extracellular matrix-associated proteins (A12 asymmetric AChE and a heparan
sulfate proteoglycan). The accumulation of AChE and BuChE into
agrin-induced aggregates occurred in the absence of any change in the
amount, rate of synthesis, accumulation, and release, or molecular forms of
either enzyme. Thus, agrin affects primarily the distribution of these
components of the postsynaptic apparatus and not their metabolism.
Agrin-induced formation of AChR aggregates was not prevented by inhibition
of protein synthesis, consistent with our previous results that
agrin-induced accumulation of AChRs occurs by lateral migration. The
accumulation of components of the extracellular matrix would seem less
likely to occur by lateral migration and so might require release of newly
synthesized proteins; indeed, formation of aggregates of heparan sulfate
proteoglycan was prevented by inhibitors of protein synthesis. Thus,
different components of the postsynaptic apparatus accumulate in agrin-
induced specializations by different mechanisms.
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