Study on a new synaptic accumulation mechanism of AMPA receptor by lipid-related molecules
| Project/Area Number |
15K08151
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General anatomy (including histology/embryology)
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| Research Institution | University of Fukui |
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Principal Investigator |
XIE MINJUE 福井大学, 子どものこころの発達研究センター, 助教 (40444210)
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| Co-Investigator(Kenkyū-buntansha) |
佐藤 真 大阪大学, 連合小児発達学研究科, 教授 (10222019)
深澤 有吾 福井大学, 学術研究院医学系部門, 教授 (60343745)
黒田 一樹 福井大学, 学術研究院医学系部門, 助教 (60557966)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Phldb2 / LTD / LTP / CamKII / PIP3 / AMPAR / CamkII / AMPA-R |
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| Outline of Final Research Achievements |
The essential involvement of phosphoinositides in synaptic plasticity is well-established, but incomplete knowledge of the downstream molecular entities prevents us from understanding it completely. Here, we determined that Phldb2, of which pleckstrin-homology domain is highly sensitive to PIP3, functions as a phosphoinositide-signaling mediator for synaptic plasticity. Phldb2 bound to postsynaptic scaffolding molecule PSD-95 and was crucial for localization and turnover of PSD-95 in the spine. Phldb2 also bound to GluA1, GluA2 and CaMKII. Phldb2 was indispensable for the interaction between NMDA receptors and CaMKII, and the synaptic density of AMPA receptors. Therefore, PIP3-responsive Phldb2 is pivotal for induction and maintenance of LTP. Phldb2 unexpectedly bound to AP2 and this was necessary for AMPA receptor endocytosis. Long-term memory formation as well as LTP and LTD was indeed impaired in our Phldb2-/- mice.
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Report
(4 results)
Research Products
(10 results)
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[Journal Article] DBZ regulates cortical cell positioning and neurite development by sustaining the anterograde transport of Lis1 and DISC1 through control of Ndel1 dual-phosphorylation.2015
Author(s)
1.Okamoto, M., Iguchi, T., Hattori, T., Matsuzaki, S., Koyama, Y., Taniguchi, M., Kodama, M., Xie, M-J., Yagi, H., Shimizu, S., Konishi, Y., Yoshimi, T., Tachibana, T., Fujieda, S., Katayama, T., Ito, A., Hirotsune, S., Tohyaman, M. and Sato, M.
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Journal Title
J Neurosci
Volume: 18
Issue: 7
Pages: 2942-2958
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Phosphoinositide responsive Phldb2 regulates synaptic plasticity2016
Author(s)
Xie MJ, Yagi H, Iguchi T, Oka Y, Fukazawa Y, Matsuzaki H, Iwata K, Ishikawa Y, Sato, M.
Organizer
The Society for Neuroscience 46th annual meeting
Place of Presentation
San Diego, USA
Year and Date
2016-11-13
Related Report
Int'l Joint Research
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