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* Department of Pharmacology, Agrin is a heparan sulfate proteoglycan that
is required for the formation and maintenance of neuromuscular junctions. During development, agrin is secreted from motor neurons to trigger the local aggregation of acetylcholine receptors (AChRs) and other proteins in the muscle fiber, which together compose
the postsynaptic apparatus. After release from the motor neuron, agrin binds to the developing muscle basal
lamina and remains associated with the synaptic portion throughout adulthood. We have recently shown that full-length chick agrin binds to a basement membrane-like preparation called MatrigelTM. The first 130 amino acids from the NH2 terminus are necessary for
the binding, and they are the reason why, on cultured
chick myotubes, AChR clusters induced by full-length agrin are small. In the current report we show that an
NH2-terminal fragment of agrin containing these 130 amino acids is sufficient to bind to MatrigelTM and that
the binding to this preparation is mediated by laminin-1.
The fragment also binds to laminin-2 and -4, the predominant laminin isoforms of the muscle fiber basal lamina. On cultured myotubes, it colocalizes with laminin and is enriched in AChR aggregates. In addition,
we show that the effect of full-length agrin on the size
of AChR clusters is reversed in the presence of the
NH2-terminal agrin fragment. These data strongly suggest that binding of agrin to laminin provides the basis
of its localization to synaptic basal lamina and other
basement membranes.
Department of Biophysical Chemistry, Biozentrum, University of Basel, CH-4056 Basel,
Switzerland
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