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

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

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dc.contributor.author Nishimune, Hiroshi
dc.contributor.author Jarad, George
dc.contributor.author Moulson, Casey L.
dc.contributor.author Müller, Ulrich
dc.contributor.author Miner, Jeffrey H.
dc.contributor.author Valdez, Gregorio
dc.contributor.author Sanes, Joshua R.
dc.date.accessioned 2010-10-06T14:45:23Z
dc.date.issued 2008
dc.identifier.citation Nishimune, Hiroshi, Gregorio Valdez, George Jarad, Casey L. Moulson, Ulrich Müller, Jeffrey H. Miner, and Joshua R. Sanes 2008. Laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junction. The Journal of Cell Biology 182(6): 1201-1215. en_US
dc.identifier.issn 0021-9525 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4459221
dc.description.abstract 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. en_US
dc.description.sponsorship Molecular and Cellular Biology en_US
dc.language.iso en_US en_US
dc.publisher The Rockefeller University Press en_US
dc.relation.isversionof doi:10.1083/jcb.200805095 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542479/pdf/ en_US
dash.license OAP
dc.title Laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junction en_US
dc.type Journal Article en_US
dc.description.version Accepted Manuscript en_US
dc.relation.journal The Journal of Cell Biology en_US
dash.depositing.author Sanes, Joshua R.
dc.date.available 2010-10-06T14:45:23Z

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  • FAS Scholarly Articles [7470]
    Peer reviewed scholarly articles from the Faculty of Arts and Sciences of Harvard University

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