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

doi:10.1038/s41598-019-40838-6

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

生理学

研究成果: Article › 査読

11 被引用数 (Scopus)

抄録

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.

本文言語	English
論文番号	4305
ジャーナル	Scientific reports
巻	9
号	1
DOI	https://doi.org/10.1038/s41598-019-40838-6
出版ステータス	Published - 2019 12月 1

ASJC Scopus subject areas

一般

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10.1038/s41598-019-40838-6

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引用スタイル

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), Article 4305. https://doi.org/10.1038/s41598-019-40838-6

Xie, MJ, 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, vol. 9, no. 1, 4305. https://doi.org/10.1038/s41598-019-40838-6

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

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.",

author = "Xie, {Min Jue} and Yasuyuki Ishikawa and Hideshi Yagi and Tokuichi Iguchi and Yuichiro Oka and Kazuki Kuroda and Keiko Iwata and Hiroshi Kiyonari and Shinji Matsuda and Hideo Matsuzaki and Michisuke Yuzaki and Yugo Fukazawa and Makoto Sato",

note = "Funding Information: We are grateful to H. Yoshikawa, S. Kanae, I. Kumano, T. Ishikawa, M. Sekiguchi and H. Miyagoshi for technical assistance, M. Yasumura for statistical analyses, T. Sheena for critical reading and to T. Taniguchi for secretarial assistance. This work was supported in part by Uehara Memorial Foundation, Takeda Science Foundation, Takeda Medical Research Foundation, Novartis Stiftung f{\"u}r Medizinisch-Biologische Forschung (Novartis Foundation for Medical-Biological Research) and a Kakenhi, from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (25293043 and 17H04014 to MS, 15k08151 and 23590232 to M-J X). Publisher Copyright: {\textcopyright} 2019, The Author(s).",

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doi = "10.1038/s41598-019-40838-6",

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T1 - PIP 3 -Phldb2 is crucial for LTP regulating synaptic NMDA and AMPA receptor density and PSD95 turnover

AU - Xie, Min Jue

AU - Ishikawa, Yasuyuki

AU - Yagi, Hideshi

AU - Iguchi, Tokuichi

AU - Oka, Yuichiro

AU - Kuroda, Kazuki

AU - Iwata, Keiko

AU - Kiyonari, Hiroshi

AU - Matsuda, Shinji

AU - Matsuzaki, Hideo

AU - Yuzaki, Michisuke

AU - Fukazawa, Yugo

AU - Sato, Makoto

N1 - Funding Information: We are grateful to H. Yoshikawa, S. Kanae, I. Kumano, T. Ishikawa, M. Sekiguchi and H. Miyagoshi for technical assistance, M. Yasumura for statistical analyses, T. Sheena for critical reading and to T. Taniguchi for secretarial assistance. This work was supported in part by Uehara Memorial Foundation, Takeda Science Foundation, Takeda Medical Research Foundation, Novartis Stiftung für Medizinisch-Biologische Forschung (Novartis Foundation for Medical-Biological Research) and a Kakenhi, from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (25293043 and 17H04014 to MS, 15k08151 and 23590232 to M-J X). Publisher Copyright: © 2019, The Author(s).

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

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

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