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...

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Main Authors:	Denzer, Alain J., Brandenberger, Ralph, Gesemann, Matthias, Chiquet, Matthias, Ruegg, Markus A.
Format:	Online
Language:	English
Published:	The Rockefeller University Press 1997
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2139873/

id	pubmed-2139873
recordtype	oai_dc
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. 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 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. 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/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Denzer, Alain J. Brandenberger, Ralph Gesemann, Matthias Chiquet, Matthias Ruegg, Markus A.
spellingShingle	Denzer, Alain J. Brandenberger, Ralph Gesemann, Matthias Chiquet, Matthias Ruegg, Markus A. Agrin Binds to the Nerve–Muscle Basal Lamina via Laminin
author_facet	Denzer, Alain J. Brandenberger, Ralph Gesemann, Matthias Chiquet, Matthias Ruegg, Markus A.
author_sort	Denzer, Alain J.
title	Agrin Binds to the Nerve–Muscle Basal Lamina via Laminin
title_short	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_sort	agrin binds to the nerve–muscle basal lamina via laminin
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 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	The Rockefeller University Press
publishDate	1997
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2139873/
_version_	1611422004740620288

Agrin Binds to the Nerve–Muscle Basal Lamina via Laminin

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