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Laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junction

A prominent feature of synaptic maturation at the neuromuscular junction (NMJ) is the topological transformation of the acetylcholine receptor (AChR)-rich postsynaptic membrane from an ovoid plaque into a complex array of branches. We show here that laminins play an autocrine role in promoting this...

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Detalles Bibliográficos
Autores principales: Nishimune, Hiroshi, Valdez, Gregorio, Jarad, George, Moulson, Casey L., Müller, Ulrich, Miner, Jeffrey H., Sanes, Joshua R.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542479/
https://www.ncbi.nlm.nih.gov/pubmed/18794334
http://dx.doi.org/10.1083/jcb.200805095
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author Nishimune, Hiroshi
Valdez, Gregorio
Jarad, George
Moulson, Casey L.
Müller, Ulrich
Miner, Jeffrey H.
Sanes, Joshua R.
author_facet Nishimune, Hiroshi
Valdez, Gregorio
Jarad, George
Moulson, Casey L.
Müller, Ulrich
Miner, Jeffrey H.
Sanes, Joshua R.
author_sort Nishimune, Hiroshi
collection PubMed
description A prominent feature of synaptic maturation at the neuromuscular junction (NMJ) is the topological transformation of the acetylcholine receptor (AChR)-rich postsynaptic membrane from an ovoid plaque into a complex array of branches. We show here that laminins play an autocrine role in promoting this transformation. Laminins containing the α4, α5, and β2 subunits are synthesized by muscle fibers and concentrated in the small portion of the basal lamina that passes through the synaptic cleft at the NMJ. Topological maturation of AChR clusters was delayed in targeted mutant mice lacking laminin α5 and arrested in mutants lacking both α4 and α5. Analysis of chimeric laminins in vivo and of mutant myotubes cultured aneurally demonstrated that the laminins act directly on muscle cells to promote postsynaptic maturation. Immunohistochemical studies in vivo and in vitro along with analysis of targeted mutants provide evidence that laminin-dependent aggregation of dystroglycan in the postsynaptic membrane is a key step in synaptic maturation. Another synaptically concentrated laminin receptor, Bcam, is dispensable. Together with previous studies implicating laminins as organizers of presynaptic differentiation, these results show that laminins coordinate post- with presynaptic maturation.
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spelling pubmed-25424792009-03-22 Laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junction Nishimune, Hiroshi Valdez, Gregorio Jarad, George Moulson, Casey L. Müller, Ulrich Miner, Jeffrey H. Sanes, Joshua R. J Cell Biol Research Articles A prominent feature of synaptic maturation at the neuromuscular junction (NMJ) is the topological transformation of the acetylcholine receptor (AChR)-rich postsynaptic membrane from an ovoid plaque into a complex array of branches. We show here that laminins play an autocrine role in promoting this transformation. Laminins containing the α4, α5, and β2 subunits are synthesized by muscle fibers and concentrated in the small portion of the basal lamina that passes through the synaptic cleft at the NMJ. Topological maturation of AChR clusters was delayed in targeted mutant mice lacking laminin α5 and arrested in mutants lacking both α4 and α5. Analysis of chimeric laminins in vivo and of mutant myotubes cultured aneurally demonstrated that the laminins act directly on muscle cells to promote postsynaptic maturation. Immunohistochemical studies in vivo and in vitro along with analysis of targeted mutants provide evidence that laminin-dependent aggregation of dystroglycan in the postsynaptic membrane is a key step in synaptic maturation. Another synaptically concentrated laminin receptor, Bcam, is dispensable. Together with previous studies implicating laminins as organizers of presynaptic differentiation, these results show that laminins coordinate post- with presynaptic maturation. The Rockefeller University Press 2008-09-22 /pmc/articles/PMC2542479/ /pubmed/18794334 http://dx.doi.org/10.1083/jcb.200805095 Text en © 2008 Nishimune et al. 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.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Nishimune, Hiroshi
Valdez, Gregorio
Jarad, George
Moulson, Casey L.
Müller, Ulrich
Miner, Jeffrey H.
Sanes, Joshua R.
Laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junction
title Laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junction
title_full Laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junction
title_fullStr Laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junction
title_full_unstemmed Laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junction
title_short Laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junction
title_sort laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junction
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542479/
https://www.ncbi.nlm.nih.gov/pubmed/18794334
http://dx.doi.org/10.1083/jcb.200805095
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