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dc.contributor.authorYoshii, Akira
dc.contributor.authorMurata, Yasunobu
dc.contributor.authorKim, Jihye
dc.contributor.authorZhang, Chao
dc.contributor.authorShokat, Kevan M.
dc.contributor.authorConstantine-Paton, Martha
dc.date.accessioned2012-05-22T20:18:28Z
dc.date.available2012-05-22T20:18:28Z
dc.date.issued2011-06
dc.date.submitted2011-06
dc.identifier.issn0270-6474
dc.identifier.issn1529-2401
dc.identifier.urihttp://hdl.handle.net/1721.1/70910
dc.description.abstractPostsynaptic density 95 (PSD-95), the major scaffold at excitatory synapses, is critical for synapse maturation and learning. In rodents, eye opening, the onset of pattern vision, triggers a rapid movement of PSD-95 from visual neuron somata to synapses. We showed previously that the PI3 kinase–Akt pathway downstream of BDNF/TrkB signaling stimulates synaptic delivery of PSD-95 via vesicular transport. However, vesicular transport requires PSD-95 palmitoylation to attach it to a lipid membrane. Also, PSD-95 insertion at synapses is known to require this lipid modification. Here, we show that BDNF/TrkB signaling is also necessary for PSD-95 palmitoylation and its transport to synapses in mouse visual cortical layer 2/3 neurons. However, palmitoylation of PSD-95 requires the activation of another pathway downstream of BDNF/TrkB, namely, signaling through phospholipase Cγ and the brain-specific PKC variant protein kinase M ζ (PKMζ). We find that PKMζ selectively regulates phosphorylation of the palmitoylation enzyme ZDHHC8. Inhibition of PKMζ results in a reduction of synaptic PSD-95 accumulation in vivo, which can be rescued by overexpressing ZDHHC8. Therefore, TrkB and PKMζ, two critical regulators of synaptic plasticity, facilitate PSD-95 targeting to synapses. These results also indicate that palmitoylation can be regulated by a trophic factor. Our findings have implications for neurodevelopmental disorders as well as aging brains.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH Grant R01EY006039-27)en_US
dc.description.sponsorshipUnited States. Dept. of Defense (Grant W81XWH-09- 1-0088)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH Grant R01EB001987)en_US
dc.language.isoen_US
dc.publisherSociety for Neuroscienceen_US
dc.relation.isversionofhttp://dx.doi.org/10.1523/jneurosci.2190-11.2011en_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.sourceSFNen_US
dc.titleTrkB and Protein Kinase M ζ Regulate Synaptic Localization of PSD-95 in Developing Cortexen_US
dc.typeArticleen_US
dc.identifier.citationYoshii, A. et al. “TrkB and Protein Kinase M ζ Regulate Synaptic Localization of PSD-95 in Developing Cortex.” Journal of Neuroscience 31.33 (2011): 11894–11904. Web.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_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.approverConstantine-Paton, Martha
dc.contributor.mitauthorConstantine-Paton, Martha
dc.contributor.mitauthorYoshii, Akira
dc.contributor.mitauthorMurata, Yasunobu
dc.contributor.mitauthorKim, Jihye
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
dspace.orderedauthorsYoshii, A.; Murata, Y.; Kim, J.; Zhang, C.; Shokat, K. M.; Constantine-Paton, M.en
dc.identifier.orcidhttps://orcid.org/0000-0003-2268-0863
mit.licensePUBLISHER_POLICYen_US


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