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Agrin Binds to the Nerve–Muscle Basal Lamina via Laminin
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 c...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
1997
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2139873/ https://www.ncbi.nlm.nih.gov/pubmed/9151673 |
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author | Denzer, Alain J. Brandenberger, Ralph Gesemann, Matthias Chiquet, Matthias Ruegg, Markus A. |
author_facet | Denzer, Alain J. Brandenberger, Ralph Gesemann, Matthias Chiquet, Matthias Ruegg, Markus A. |
author_sort | Denzer, Alain J. |
collection | PubMed |
description | 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 NH(2) 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 NH(2)-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 NH(2)-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. |
format | Text |
id | pubmed-2139873 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1997 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21398732008-05-01 Agrin Binds to the Nerve–Muscle Basal Lamina via Laminin Denzer, Alain J. Brandenberger, Ralph Gesemann, Matthias Chiquet, Matthias Ruegg, Markus A. J Cell Biol Article 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 NH(2) 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 NH(2)-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 NH(2)-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. The Rockefeller University Press 1997-05-05 /pmc/articles/PMC2139873/ /pubmed/9151673 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Denzer, Alain J. Brandenberger, Ralph Gesemann, Matthias Chiquet, Matthias Ruegg, Markus A. Agrin Binds to the Nerve–Muscle Basal Lamina via Laminin |
title | Agrin Binds to the Nerve–Muscle Basal Lamina via Laminin |
title_full | Agrin Binds to the Nerve–Muscle Basal Lamina via Laminin |
title_fullStr | Agrin Binds to the Nerve–Muscle Basal Lamina via Laminin |
title_full_unstemmed | Agrin Binds to the Nerve–Muscle Basal Lamina via Laminin |
title_short | Agrin Binds to the Nerve–Muscle Basal Lamina via Laminin |
title_sort | agrin binds to the nerve–muscle basal lamina via laminin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2139873/ https://www.ncbi.nlm.nih.gov/pubmed/9151673 |
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