Study on a new synaptic accumulation mechanism of AMPA receptor by lipid-related molecules

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08151
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: University of Fukui
• 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)
• 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)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: Phldb2 / LTD / LTP / CamKII / PIP3 / AMPAR

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.

Free Research Field

医歯薬学