PIP 3 -Phldb2 is crucial for LTP regulating synaptic NMDA and AMPA receptor density and PSD95 turnover

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

Research output: Contribution to journalArticle

Abstract

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 PIP 3 , 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, PIP 3 -responsive Phldb2 is pivotal for induction and maintenance of LTP. Memory formation was impaired in our Phldb2 −/− mice.

Original languageEnglish
Article number4305
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

ASJC Scopus subject areas

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    Xie, M. J., Ishikawa, Y., Yagi, H., Iguchi, T., Oka, Y., Kuroda, K., Iwata, K., Kiyonari, H., Matsuda, S., Matsuzaki, H., Yuzaki, M., Fukazawa, Y., & Sato, M. (2019). PIP 3 -Phldb2 is crucial for LTP regulating synaptic NMDA and AMPA receptor density and PSD95 turnover Scientific reports, 9(1), [4305]. https://doi.org/10.1038/s41598-019-40838-6