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dc.contributor.authorvan Zundert, B.
dc.contributor.authorYoshii, Akira
dc.contributor.authorZhao, Jian-Ping
dc.contributor.authorPandian, Swarna
dc.contributor.authorConstantine-Paton, Martha
dc.date.accessioned2017-11-20T16:38:08Z
dc.date.available2017-11-20T16:38:08Z
dc.date.issued2013-05
dc.date.submitted2013-03
dc.identifier.issn0270-6474
dc.identifier.issn1529-2401
dc.identifier.urihttp://hdl.handle.net/1721.1/112239
dc.description.abstractMyosin Va (MyoVa) mediates F-actin-based vesicular transport toward the plasma membrane and is found at neuronal postsynaptic densities (PSDs), but the role of MyoVa in synaptic development and function is largely unknown. Here, in studies using the dominantnegative MyoVa neurological mutant mouse Flailer, we find that MyoVa plays an essential role in activity-dependent delivery of PSD-95 and other critical PSD molecules to synapses and in endocytosis of AMPA-type glutamate receptors (AMPAR) in the dendrites of CNS neurons. MyoVa is known to carry a complex containing the major scaffolding proteins of the mature PSD, PSD-95, SAPAP1/GKAP, Shank, and Homer to dendritic spine synapses. In Flailer, neurons show abnormal dendritic shaft localization of PSD-95, stargazin, dynamin3, AMPARs and abnormal spine morphology. Flailer neurons also have abnormally highAMPARminiature current frequencies and spontaneous AMPAR currents that are more frequent and larger than in wild-type while numbers of NMDAR containing synapses remain normal. The AMPAR abnormalities are consistent with a severely disrupted developmental regulation of long-term depression that we find in cortical Flailer neurons. Thus MyoVa plays a fundamentally important role both in localizing mature glutamate synapses to spines and in organizing the synapse for normal function. For this reason Flailer mice will be valuable in further dissecting the role of MyoVa in normal synaptic and circuit refinement and also in studies of neurological and neuropsychiatric diseases where disruptions of normal glutamate synapses are frequently observed.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant R01-EY014074–17)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant EY014420)en_US
dc.publisherSociety for Neuroscienceen_US
dc.relation.isversionofhttp://dx.doi.org/10.1523/JNEUROSCI.4585-12.2013en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourceSociety for Neuroscienceen_US
dc.titleA Myosin Va Mutant Mouse with Disruptions in Glutamate Synaptic Development and Mature Plasticity in Visual Cortexen_US
dc.typeArticleen_US
dc.identifier.citationYoshii, A. et al. “A Myosin Va Mutant Mouse with Disruptions in Glutamate Synaptic Development and Mature Plasticity in Visual Cortex.” Journal of Neuroscience 33, 19 (May 2013): 8472–8482 © 2013 The Author(s)en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciencesen_US
dc.contributor.departmentMcGovern Institute for Brain Research at MITen_US
dc.contributor.mitauthorYoshii, Akira
dc.contributor.mitauthorZhao, Jian-Ping
dc.contributor.mitauthorPandian, Swarna
dc.contributor.mitauthorConstantine-Paton, Martha
dc.relation.journalJournal of Neuroscienceen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2017-11-01T18:39:46Z
dspace.orderedauthorsYoshii, A.; Zhao, J.-P.; Pandian, S.; van Zundert, B.; Constantine-Paton, M.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0003-4308-7073
dc.identifier.orcidhttps://orcid.org/0000-0003-2268-0863
mit.licensePUBLISHER_POLICYen_US
mit.metadata.statusComplete


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