dc.contributor.author | Samuel, Melanie Ann | |
dc.contributor.author | Valdez, Gregorio | |
dc.contributor.author | Tapia, Juan | |
dc.contributor.author | Lichtman, Jeff | |
dc.contributor.author | Sanes, Joshua R. | |
dc.date.accessioned | 2014-02-21T20:08:46Z | |
dc.date.issued | 2012 | |
dc.identifier.citation | Samuel, Melanie A., Gregorio Valdez, Juan C. Tapia, Jeff W. Lichtman, and Joshua R. Sanes. 2012. Agrin and synaptic laminin are required to maintain adult neuromuscular junctions. PLoS ONE 7(10): e46663. | en_US |
dc.identifier.issn | 1932-6203 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:11729591 | |
dc.description.abstract | As 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-α4 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_US |
dc.description.sponsorship | Molecular and Cellular Biology | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Public Library of Science | en_US |
dc.relation.isversionof | doi:10.1371/journal.pone.0046663 | en_US |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3463559/pdf/ | en_US |
dash.license | LAA | |
dc.subject | Biology | en_US |
dc.subject | Anatomy and Physiology | en_US |
dc.subject | Neurological System | en_US |
dc.subject | Synapses | en_US |
dc.subject | Molecular Cell Biology | en_US |
dc.subject | Extracellular Matrix | en_US |
dc.subject | Basement Membrane | en_US |
dc.subject | Extracellular Matrix Composition | en_US |
dc.subject | Cell Adhesion | en_US |
dc.subject | Neuroscience | en_US |
dc.subject | Cellular Neuroscience | en_US |
dc.subject | Neuronal Morphology | en_US |
dc.subject | Motor Systems | en_US |
dc.subject | Neurobiology of Disease and Regeneration | en_US |
dc.subject | Medicine | en_US |
dc.subject | Neurology | en_US |
dc.subject | Neuromuscular Diseases | en_US |
dc.title | Agrin and Synaptic Laminin Are Required to Maintain Adult Neuromuscular Junctions | en_US |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en_US |
dc.relation.journal | PLoS ONE | en_US |
dash.depositing.author | Sanes, Joshua R. | |
dc.date.available | 2014-02-21T20:08:46Z | |
dc.identifier.doi | 10.1371/journal.pone.0046663 | * |
dash.contributor.affiliated | Samuel, Melanie Ann | |
dash.contributor.affiliated | Tapia, Juan | |
dash.contributor.affiliated | Sanes, Joshua | |
dash.contributor.affiliated | Valdez, Gregorio | |
dash.contributor.affiliated | Lichtman, Jeff | |