DC Field | Value | Language |
---|---|---|
dc.contributor.author | Han, Kyung Ah | ko |
dc.contributor.author | Woo, Doyeon | ko |
dc.contributor.author | Kim, Seungjoon | ko |
dc.contributor.author | Choii, Gayoung | ko |
dc.contributor.author | Jeon, Sangmin | ko |
dc.contributor.author | Won, Seoung Youn | ko |
dc.contributor.author | Kim, Ho Min | ko |
dc.contributor.author | Heo, Won Do | ko |
dc.contributor.author | Um, Ji Won | ko |
dc.contributor.author | Ko, Jaewon | ko |
dc.date.accessioned | 2016-07-05T08:21:16Z | - |
dc.date.available | 2016-07-05T08:21:16Z | - |
dc.date.created | 2016-05-31 | - |
dc.date.created | 2016-05-31 | - |
dc.date.created | 2016-05-31 | - |
dc.date.issued | 2016-04 | - |
dc.identifier.citation | JOURNAL OF NEUROSCIENCE, v.36, no.17, pp.4816 - 4831 | - |
dc.identifier.issn | 0270-6474 | - |
dc.identifier.uri | http://hdl.handle.net/10203/209349 | - |
dc.description.abstract | Neurotrophin-3 (NT-3) is a secreted neurotrophic factor that binds neurotrophin receptor tyrosine kinase C (TrkC), which in turn binds to presynaptic protein tyrosine phosphatase sigma (PTP sigma) to govern excitatory synapse development. However, whether and how NT-3 cooperates with the TrkC-PTP sigma synaptic adhesion pathway and TrkC-mediated intracellular signaling pathways in rat cultured neurons has remained unclear. Here, we report that NT-3 enhances TrkC binding affinity for PTP sigma. Strikingly, NT-3 treatment bidirectionally regulates the synaptogenic activity of TrkC: at concentrations of 10-25 ng/ml, NT-3 further enhanced the increase in synapse density induced by TrkC overexpression, whereas at higher concentrations, NT-3 abrogated TrkC-induced increases in synapse density. Semi-quantitative immunoblotting and optogenetics-based imaging showed that 25 ng/ml NT-3 or light stimulation at a power that produced a comparable level of NT-3 (6.25 mu W) activated only extracellular signal-regulated kinase (ERK) and Akt, whereas 100 ng/ml NT-3 (light intensity, 25 mu W) further triggered the activation of phospholipase C-gamma 1 and CREB independently of PTP sigma. Notably, disruption of TrkC intracellular signaling pathways, extracellular ligand binding, or kinase activity by point mutations compromised TrkC-induced increases in synapse density. Furthermore, only sparse, but not global, TrkC knock-down in cultured rat neurons significantly decreased synapse density, suggesting that intercellular differences in TrkC expression level are critical for its synapse-promoting action. Together, our data demonstrate that NT-3 is a key factor in excitatory synapse development that may direct higher-order assembly of the TrkC/PTP sigma complex and activate distinct intracellular signaling cascades in a concentration-dependent manner to promote competition-based synapse development processes | - |
dc.language | English | - |
dc.publisher | SOC NEUROSCIENCE | - |
dc.title | Neurotrophin-3 Regulates Synapse Development by Modulating TrkC-PTP sigma Synaptic Adhesion and Intracellular Signaling Pathways | - |
dc.type | Article | - |
dc.identifier.wosid | 000375130500015 | - |
dc.identifier.scopusid | 2-s2.0-84966667386 | - |
dc.type.rims | ART | - |
dc.citation.volume | 36 | - |
dc.citation.issue | 17 | - |
dc.citation.beginningpage | 4816 | - |
dc.citation.endingpage | 4831 | - |
dc.citation.publicationname | JOURNAL OF NEUROSCIENCE | - |
dc.identifier.doi | 10.1523/JNEUROSCI.4024-15.2016 | - |
dc.contributor.localauthor | Kim, Ho Min | - |
dc.contributor.localauthor | Heo, Won Do | - |
dc.contributor.nonIdAuthor | Han, Kyung Ah | - |
dc.contributor.nonIdAuthor | Kim, Seungjoon | - |
dc.contributor.nonIdAuthor | Choii, Gayoung | - |
dc.contributor.nonIdAuthor | Jeon, Sangmin | - |
dc.contributor.nonIdAuthor | Won, Seoung Youn | - |
dc.contributor.nonIdAuthor | Um, Ji Won | - |
dc.contributor.nonIdAuthor | Ko, Jaewon | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | excitatory synapse | - |
dc.subject.keywordAuthor | neurotrophin-3 | - |
dc.subject.keywordAuthor | PTP sigma | - |
dc.subject.keywordAuthor | synaptic cell adhesion | - |
dc.subject.keywordAuthor | TrkC | - |
dc.subject.keywordPlus | HIPPOCAMPAL-NEURONS | - |
dc.subject.keywordPlus | STRUCTURAL BASIS | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | COMPLEX | - |
dc.subject.keywordPlus | MOLECULES | - |
dc.subject.keywordPlus | SYNAPTOGENESIS | - |
dc.subject.keywordPlus | COMPETITION | - |
dc.subject.keywordPlus | ORGANIZERS | - |
dc.subject.keywordPlus | SLITRKS | - |
dc.subject.keywordPlus | DEPENDS | - |
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