Remodeling of the postsynaptic density during postnatal development

• Project/Area Number: 18K14830
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Kobe University (2020-2021); Institute of Physical and Chemical Research (2018-2019)
• Principal Investigator: Kaizuka Takeshi 神戸大学, 医学研究科, 特命助教 (40782032)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: PSD / シナプス後肥厚 / シナプス / プロテオミクス / 自閉症 / 自閉スペクトラム症 / 液-液相分離 / 霊長類 / 樹状突起スパイン / 神経回路形成 / ニューロン

Outline of Final Research Achievements

I analyzed protein composition of the postsynaptic density (PSD) by proteome analysis. During postnatal development, protein involved in synaptic plasticity is found to be significantly increased or decreased in PSD in mouse brain. This is accompanied with altered signal transduction. Correlations with the transcriptome datasets suggested that the increase or decrease in protein levels after 2-week-old mouse is caused by changes in gene expression that occur after postnatal day 4. Similar protein increases and decreases were suggested to occur around birth in primates. Analysis of transcriptome dataset of the patient with autism spectrum disorders suggested that the composition of PSD is more immature in patient brain. I also found that alteration of PSD composition in common marmoset brain after 2-month-old is distinct from that found in postnatal mouse brain.

Academic Significance and Societal Importance of the Research Achievements

本研究では、生後発達期のシナプスのタンパク質組成の変化を網羅的に明らかにし、それがどのような意義を持っているか、またどのようなメカニズムにより生じていると考えられるかを示した。これらの結果は、シナプスの成熟を「タンパク質組成」の観点からとらえる考え方を提供したとも言える。また、自閉症などの神経発達障害にもシナプスのタンパク質組成の異常（成熟不全）が関与している可能性を示した。社会的には、自閉症の治療戦略への考え方を提供したという点でも意義があるのではないかと考えている。

Research Products

• [Journal Article] Developmental dynamics of the postsynaptic proteome to understand synaptic maturation and dysmaturation (2022)
  • Author(s): Takeshi Kaizuka, Takehiro Suzuki, Noriyuki Kishi, Manfred W. Kilimann, Takehiko Ueyama, Masahiko Watanabe, Hideyuki Okano, Naoshi Dohmae, Toru Takumi
  • Journal Title: bioRxiv Volume: なし Pages: 1-55
  • DOI: 10.1101/2022.05.05.490828
  • Open Access / Int'l Joint Research
• [Journal Article] Autophagy is required for maturation of surfactant-containing lamellar bodies in the lung and swim bladder (2020)
  • Author(s): Hideaki Morishita, Yuki Kanda, Takeshi Kaizuka, Haruka Chino, Kazuki Nakao, Yoshimi Miki, Yoshitaka Taketomi, Jun-Lin Guan, Makoto Murakami, Atsu Aiba, Noboru Mizushima
  • Journal Title: Cell Reports Volume: 33 Issue: 10 Pages: 108477-108477
  • DOI: 10.1016/j.celrep.2020.108477
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 発達期のげっ歯類および霊長類の脳におけるシナプス後肥厚のリモデリング (2020)
  • Author(s): 貝塚 剛志、鈴木 健裕、岸 憲幸、堂前 直、岡野 栄之、内匠 透
  • Organizer: 第93回日本生化学会大会
• [Presentation] 発達期におけるシナプス後肥厚のリモデリング (2019)
  • Author(s): 貝塚 剛志、鈴木 健裕、堂前 直、内匠 透
  • Organizer: 日本プロテオーム学会2019年大会・第70回日本電気泳動学会総会
• [Presentation] 発達期の脳におけるシナプス後肥厚のリモデリング (2019)
  • Author(s): 貝塚 剛志
  • Organizer: 次世代脳プロジェクト 冬のシンポジウム
• [Presentation] Remodeling of PSD composition during postnatal development (2018)
  • Author(s): Takeshi Kaizuka, Toru Takumi
  • Organizer: Cold Spring Harbor Asia, Autism & Neurodevelopment Disorders
  • Int'l Joint Research
• [Presentation] Remodeling of postsynaptic density during development (2018)
  • Author(s): Takeshi Kaizuka, Toru Takumi
  • Organizer: 文部科学省新学術領域研究「スクラップ＆ビルドによる脳機能の動的制御」第2回領域会議