Agrin binds to the nerve-muscle basal lamina via laminin
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID 155392
Author(s) Denzer, A J; Brandenberger, R; Gesemann, M; Chiquet, M; Ruegg, M A
Author(s) at UniBasel Rüegg, Markus A.
Year 1997
Title Agrin binds to the nerve-muscle basal lamina via laminin
Journal The Journal of cell biology
Volume 137
Number 3
Pages / Article-Number 671-83
Keywords Agrin/*chemistry/*metabolism; Amino Acid Sequence; Animals; Basement Membrane/*metabolism; Binding Sites; COS Cells; Cells; Cultured; Chick Embryo; Collagen; Drug Combinations; Extracellular Matrix/metabolism; Humans; Laminin/*metabolism; Mice; Molecular Sequence Data; Neuromuscular Junction/metabolism; Peptide Fragments/metabolism; Protein Binding; Proteoglycans; Receptor Aggregation; Receptors; Nicotinic/metabolism; Retina/metabolism; Sequence Alignment; Sequence Homology; Amino Acid; Structure-Activity Relationship

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 Matrigel. 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 Matrigel 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.

Publisher Rockefeller University Press
ISSN/ISBN 0021-9525
Full Text on edoc Available
Digital Object Identifier DOI 10.1083/jcb.137.3.671
PubMed ID
ISI-Number WOS:A1997WY01900012
Document type (ISI) Journal Article

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