Analysis of modulatory effects of Pin1 on DARPP-32 function.

• Project/Area Number: 24791220
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Fukushima Medical University
• Principal Investigator: HINO MIZUKI 福島県立医科大学, 医学部, 研究員 (80396663)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: DARPP-32 / Pin1 / 統合失調症 / リン酸化 / DARP32 / DARPP32

Outline of Final Research Achievements

DARPP-32, which is thought to be involved in schizophrenia, controls the protein phosphatase (PP1) and protein kinase A (PKA) in a phosphorylation-dependent manner, and its phosphorylation level is regulated by dopaminergic and glutaminergic stimulations. .
We hypothesize that Pin1 isomerizes phosphorylated DARPP-32 and controls the inhibitory activity of DARPP-32 on PP1 and PKA. We conducted biochemical analysis to examine the hypothesis. We also made in silico analysis to predict the common binding partners of DARPP-32 and Pin1.

Research Products

• [Journal Article] Elevated postmortem striatal t-DARPP expression in schizophrenia and associations with DRD2/ANKK1 polymorphism (2014)
  • Author(s): Kunii Y, Miura I, Matsumoto J, Hino M, Wada A, Niwa SI, Nawa H, Sakai M, Someya T, Takahashi H, Kakita A, Yabe H.
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry Volume: 5846(14)(Epub ahead of print) Pages: 123-128
  • DOI: 10.1016/j.pnpbp.2014.03.014
  • Peer Reviewed / Open Access
• [Journal Article] X irradiation changes dendritic spine morphology and density through reduction of cytoskeletal proteins in mature neurons. (2013)
  • Author(s): Shirai K, Mizui T, Suzuki Y, Okamoto M, Hanamura K, Yoshida Y, Hino M, Noda SE, Al-jahdari WS, Chakravarti A, Shirao T, Nakano T.
  • Journal Title: Radiat Res. Volume: 179 Issue: 6 Pages: 630-6
  • DOI: 10.1667/rr3098.1
  • Peer Reviewed
• [Presentation] 統合失調症患者死後脳前頭前皮質におけるAktシグナル伝達系蛋白質群の多項目同時測定 (2016)
  • Author(s): 日野瑞城 國井泰人 松本純弥 和田明 長岡敦子 丹羽真一 高橋均 柿田明美 赤津裕康 堀映 橋詰良夫 山本孝之 矢部博興
  • Organizer: 日本統合失調症学会
  • Place of Presentation: 群馬県前橋市
  • Year and Date: 2016-03-25
• [Presentation] 統合失調症死後脳内タンパク質発現解析および 発現量が変動したタンパク質の局在解析; 質量分析法による網羅的及び標的指向的な二種の定量解析を用いて (2014)
  • Author(s): 國井泰人,大槻純男,瀧澤陽平,日野瑞城,松本純弥,和田明,赤津裕康,橋詰良夫,山本孝之, 瀬藤光利, 寺崎哲也,丹羽真一,矢部博興
  • Organizer: 統合失調症学会
  • Place of Presentation: 京都