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PIP 3 -Phldb2 is crucial for LTP regulating synaptic NMDA and AMPA receptor density and PSD95 turnover
Scientific Reports ( IF 3.8 ) Pub Date : 2019-03-13 , DOI: 10.1038/s41598-019-40838-6
Min-Jue Xie , Yasuyuki Ishikawa , Hideshi Yagi , Tokuichi Iguchi , Yuichiro Oka , Kazuki Kuroda , Keiko Iwata , Hiroshi Kiyonari , Shinji Matsuda , Hideo Matsuzaki , Michisuke Yuzaki , Yugo Fukazawa , Makoto Sato

The essential involvement of phosphoinositides in synaptic plasticity is well-established, but incomplete knowledge of the downstream molecular entities prevents us from understanding their signalling cascades completely. Here, we determined that Phldb2, of which pleckstrin-homology domain is highly sensitive to PIP3, functions as a phosphoinositide-signalling mediator for synaptic plasticity. BDNF application caused Phldb2 recruitment toward postsynaptic membrane in dendritic spines, whereas PI3K inhibition resulted in its reduced accumulation. 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 and GluA2. 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. Memory formation was impaired in our Phldb2−/− mice.



中文翻译:

PIP 3 -Phldb2对于LTP调节突触NMDA和AMPA受体密度以及PSD95转换至关重要

磷酸肌醇在突触可塑性中的基本参与是众所周知的,但是对下游分子实体的不完全了解使我们无法完全理解其信号级联。在这里,我们确定其中pleckstrin同源域Phldb2对PIP 3高度敏感,作为磷酸肌醇信号传导介质,用于突触可塑性。BDNF的应用导致Phldb2在树突棘中向突触后膜募集,而PI3K抑制导致其积累减少。Phldb2绑定到突触后支架分子PSD-95,并且对脊柱中PSD-95的定位和更新至关重要。Phldb2也绑定到GluA1和GluA2。Phldb2对于NMDA受体和CaMKII之间的相互作用以及AMPA受体的突触密度是必不可少的。因此,PIP 3反应性Phldb2对于LTP的诱导和维持至关重要。在我们的Phldb2 -/-小鼠中记忆形成受到损害。

更新日期:2019-03-13
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