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Agrin and Synaptic Laminin Are Required to Maintain Adult Neuromuscular Junctions

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dc.contributor.authorSamuel, Melanieen
dc.contributor.authorValdez, Gregorioen
dc.contributor.authorTapia, Juan C.en
dc.contributor.authorLichtman, Jeff W.en
dc.contributor.authorSanes, Joshua R.en
dc.date.accessioned2018-11-19T18:32:10Zen
dc.date.available2018-11-19T18:32:10Zen
dc.date.issued2012-10-03en
dc.description.abstractAs synapses form and mature the synaptic partners produce organizing molecules that regulate each other’s differentiation and ensure precise apposition of pre- and post-synaptic specializations. At the skeletal neuromuscular junction (NMJ), these molecules include agrin, a nerve-derived organizer of postsynaptic differentiation, and synaptic laminins, muscle-derived organizers of presynaptic differentiation. Both become concentrated in the synaptic cleft as the NMJ develops and are retained in adulthood. Here, we used mutant mice to ask whether these organizers are also required for synaptic maintenance. Deletion of agrin from a subset of adult motor neurons resulted in the loss of acetylcholine receptors and other components of the postsynaptic apparatus and synaptic cleft. Nerve terminals also atrophied and eventually withdrew from muscle fibers. On the other hand, mice lacking the presynaptic organizer laminin-a4 retained most of the synaptic cleft components but exhibited synaptic alterations reminiscent of those observed in aged animals. Although we detected no marked decrease in laminin or agrin levels at aged NMJs, we observed alterations in the distribution and organization of these synaptic cleft components suggesting that such changes could contribute to age-related synaptic disassembly. Together, these results demonstrate that pre- and post-synaptic organizers actively function to maintain the structure and function of adult NMJs.en
dc.description.sponsorshipNational Institute of Healthen
dc.description.sponsorshipNIH: R01AG32322en
dc.description.sponsorshipNIH: R01NS59853en
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0046663en
dc.identifier.issue10en
dc.identifier.urihttp://hdl.handle.net/10919/85897en
dc.identifier.volume7en
dc.language.isoen_USen
dc.publisherPLOSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleAgrin and Synaptic Laminin Are Required to Maintain Adult Neuromuscular Junctionsen
dc.title.serialPLOS Oneen
dc.typeArticle - Refereeden
dc.type.dcmitypetexten

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