Role of Reelin regulating Golgi apparatus dynamics in neuronal development

• Project/Area Number: 15K06795
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Institute for Developmental Research, Aichi Human Service Center
• Principal Investigator: Matsuki Tohru 愛知県心身障害者コロニー発達障害研究所, 発生障害学部, 主任研究員 (90332329)
• Research Collaborator: Nakayama Atsuo ; Howell Brian W.
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: Reelin / ゴルジ体 / 神経細胞移動 / 細胞極性 / リン酸化 / Reelinシグナル / 神経分化 / PKC / Stk25 / GM130 / ゴルジ体ダイナミクス / 神経細胞の発達

Outline of Final Research Achievements

Neuronal migration during cortical lamination is precisely regulated and necessary for development of functional brain. Reelin siganling and Stk25 are known to be involved in neuronal development.In this study, we identified that Reelin triggers GM130, a Golgi apparatus molecule, phosphorylation through PKC activation. Furthermore, this stimuli induces Golgi deployment and dendrite extension. On the other hand, MST3, a family member of STK25, compensates for STK25 regulating biological phenomenon. These molecules interact with Rac1, a member of Rho-GTPases. In addition, Stk25 and MST3 accelerate degradation of RhoA through the interaction.
This study demonstrates that Stk25 and MST3 act as hub proteins for Rac1 activation and RhoA destabilization pathway and also provides insights not only for uncovering roles of GCKIII proteins, but also for understanding the basis of the cortical layer formation.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、大脳皮質の発達機構を根本から理解する上で非常に重要な知見をもたらしている。特に、組織形態的に問題がない知的障害を初めとする発達障害では、神経細胞の発達機構が発達過程、発達後の神経機能に大きな影響を与える事が多いため、今回の知見が関連疾患の理解にも繋がる事が期待される。

Research Products

• [Int'l Joint Research] SUNY, Upstate Medical University(米国)
• [Presentation] Stk25 and MST3 act on neuronal polarization and migration in a compensation manner. (2018)
  • Author(s): 松木亨
  • Organizer: 日本神経科学学会
• [Presentation] Stk25 and MST3 act on neuronal polarization, migration, and cardiovascular development with compensation manner. (2018)
  • Author(s): 松木亨、飯尾明生、上田昌史、戸谷明恵、中山敦雄
  • Organizer: 平成29年度「先端モデル動物支援」成果発表会
• [Presentation] Stk25欠損マウスの発達においてMST3が果たす代償的役割 (2017)
  • Author(s): 松木亨、飯尾明生、中山敦雄
  • Organizer: 日本組織培養学会第90回大会
• [Presentation] 神経極性制御に関わるStk25-LKB1シグナルが神経系の発達と機能に果たす役割 (2016)
  • Author(s): 松木亨
  • Organizer: 日本組織培養学会第89回大会
  • Place of Presentation: 大阪
• [Presentation] 神経極性制御に関わるStk25-LKB1シグナルが神経系の発達と機能に果たす役割 (2016)
  • Author(s): 松木亨
  • Organizer: シンポジウム 培養神経細胞の可能性 「医薬品開発への応用を目指したモデル細胞の構築とその応用」
  • Place of Presentation: 大阪
  • Invited
• [Presentation] 発達障害研究のための歯髄幹細胞バンクの構築 (2015)
  • Author(s): 松木亨
  • Organizer: 日本組織培養学会 第88回大会
  • Place of Presentation: 広島大学
  • Year and Date: 2015-05-26