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Article: Kinesin-1 Regulates Extrasynaptic Targeting of NMDARs and Neuronal Vulnerability Toward Excitotoxicity
Title | Kinesin-1 Regulates Extrasynaptic Targeting of NMDARs and Neuronal Vulnerability Toward Excitotoxicity |
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Authors | |
Keywords | Cellular Neuroscience Molecular Neuroscience Neuroscience |
Issue Date | 2019 |
Publisher | Cell Press. The Journal's web site is located at https://www.cell.com/iscience.home |
Citation | iScience, 2019, v. 13, p. 82-97 How to Cite? |
Abstract | N-methyl-D-aspartate (NMDA) receptor (NMDAR) is highly compartmentalized in neurons, and its dysfunction has been implicated in various neuropsychiatric and neurodegenerative disorders. Recent failure to exploit NMDAR antagonization as a potential therapeutic target has driven the need to identify molecular mechanisms that regulate NMDAR compartmentalization. Here, we report that the reduction of Kif5b, the heavy chain of kinesin-1, protected neurons against NMDA-induced excitotoxicity and ischemia-provoked neurodegeneration. Direct binding of kinesin-1 to the GluN2B cytoplasmic tails regulated the levels of NMDAR at extrasynaptic sites and the subsequent influx of calcium mediated by extrasynaptic NMDAR by regulating the insertion of NMDARs into neuronal surface. Transient increase of Kif5b restored the surface levels of NMDAR and the decreased neuronal susceptibility to NMDA-induced excitotoxicity. The expression of Kif5b was repressed in cerebral ischemia preconditioning. Our findings reveal that kinesin-1 regulates extrasynaptic NMDAR targeting and signaling, and the reduction of kinesin-1 could be exploited to defer neurodegeneration. |
Persistent Identifier | http://hdl.handle.net/10722/270049 |
ISSN | 2023 Impact Factor: 4.6 2023 SCImago Journal Rankings: 1.497 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Lin, R | - |
dc.contributor.author | Duan, Z | - |
dc.contributor.author | Sun, H | - |
dc.contributor.author | Fung, ML | - |
dc.contributor.author | Chen, H | - |
dc.contributor.author | Wang, J | - |
dc.contributor.author | Lau, CF | - |
dc.contributor.author | Yang, D | - |
dc.contributor.author | Liu, Y | - |
dc.contributor.author | Ni, Y | - |
dc.contributor.author | Wang, Z | - |
dc.contributor.author | Cui, J | - |
dc.contributor.author | Wu, W | - |
dc.contributor.author | Yung, WH | - |
dc.contributor.author | Chan, YS | - |
dc.contributor.author | Lo, ACY | - |
dc.contributor.author | Xia, J | - |
dc.contributor.author | Shen, J | - |
dc.contributor.author | Huang, J | - |
dc.date.accessioned | 2019-05-20T05:08:26Z | - |
dc.date.available | 2019-05-20T05:08:26Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | iScience, 2019, v. 13, p. 82-97 | - |
dc.identifier.issn | 2589-0042 | - |
dc.identifier.uri | http://hdl.handle.net/10722/270049 | - |
dc.description.abstract | N-methyl-D-aspartate (NMDA) receptor (NMDAR) is highly compartmentalized in neurons, and its dysfunction has been implicated in various neuropsychiatric and neurodegenerative disorders. Recent failure to exploit NMDAR antagonization as a potential therapeutic target has driven the need to identify molecular mechanisms that regulate NMDAR compartmentalization. Here, we report that the reduction of Kif5b, the heavy chain of kinesin-1, protected neurons against NMDA-induced excitotoxicity and ischemia-provoked neurodegeneration. Direct binding of kinesin-1 to the GluN2B cytoplasmic tails regulated the levels of NMDAR at extrasynaptic sites and the subsequent influx of calcium mediated by extrasynaptic NMDAR by regulating the insertion of NMDARs into neuronal surface. Transient increase of Kif5b restored the surface levels of NMDAR and the decreased neuronal susceptibility to NMDA-induced excitotoxicity. The expression of Kif5b was repressed in cerebral ischemia preconditioning. Our findings reveal that kinesin-1 regulates extrasynaptic NMDAR targeting and signaling, and the reduction of kinesin-1 could be exploited to defer neurodegeneration. | - |
dc.language | eng | - |
dc.publisher | Cell Press. The Journal's web site is located at https://www.cell.com/iscience.home | - |
dc.relation.ispartof | iScience | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Cellular Neuroscience | - |
dc.subject | Molecular Neuroscience | - |
dc.subject | Neuroscience | - |
dc.title | Kinesin-1 Regulates Extrasynaptic Targeting of NMDARs and Neuronal Vulnerability Toward Excitotoxicity | - |
dc.type | Article | - |
dc.identifier.email | Sun, H: haitao88@hku.hk | - |
dc.identifier.email | Fung, ML: fungml@hku.hk | - |
dc.identifier.email | Chen, H: chenhs@hku.hk | - |
dc.identifier.email | Chan, YS: yschan@hku.hk | - |
dc.identifier.email | Lo, ACY: amylo@hku.hk | - |
dc.identifier.email | Shen, J: shenjg@hku.hk | - |
dc.identifier.email | Huang, J: jdhuang@hku.hk | - |
dc.identifier.authority | Fung, ML=rp00433 | - |
dc.identifier.authority | Wu, W=rp00419 | - |
dc.identifier.authority | Chan, YS=rp00318 | - |
dc.identifier.authority | Lo, ACY=rp00425 | - |
dc.identifier.authority | Shen, J=rp00487 | - |
dc.identifier.authority | Huang, J=rp00451 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1016/j.isci.2019.02.009 | - |
dc.identifier.scopus | eid_2-s2.0-85066290235 | - |
dc.identifier.hkuros | 297828 | - |
dc.identifier.volume | 13 | - |
dc.identifier.spage | 82 | - |
dc.identifier.epage | 97 | - |
dc.identifier.isi | WOS:000462829500008 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 2589-0042 | - |