Synapse maintenance by afadin and its binding proteins

• Project/Area Number: 16K19036
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Kobe University
• Principal Investigator: Maruo Tomohiko 神戸大学, 医学研究科, 医学研究員 (10625114)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 海馬苔状線維シナプス / 加齢 / アファディン / ネクチン / マギン / シナプス / パンクタアドヘレンティアジャンクション / 神経シナプス

Outline of Final Research Achievements

The investigations using knockout mice of afadin and its binding protein MAGUIN revealed that proteins localized at puncta adherentia junctions (PAJs) regulate synapse formation, maintenance, and resultant functions. On the other hand, synaptic junctions and PAJs are unexpectedly stable in the aged mouse hippocampus under the normal housing condition. There were quantitative alterations, to some extent, of PAJ protein accumulation at the sites of the hippocampal giant mossy fiber synapses, although further experiments would be required to clarify the functional significance of these changes. Toward this aim, I will study aged-afadin and MAGUIN knockout mice, and mouse models in which PAJ protein accumulation is affected.

Research Products

• [Journal Article] Requirement of the F-actin-binding activity of l-afadin for enhancing the formation of adherens and tight junctions (2018)
  • Author(s): Sakakibara Shotaro、Maruo Tomohiko、Miyata Muneaki、Mizutani Kiyohito、Takai Yoshimi
  • Journal Title: Genes to Cells Volume: 23 Issue: 3 Pages: 185-199
  • DOI: 10.1111/gtc.12566
  • Peer Reviewed
• [Journal Article] Multiple Roles of Afadin in the Ultrastructural Morphogenesis of Mouse Hippocampal Mossy Fiber Synapses. (2017)
  • Author(s): Sai K, Wang S, Kaito A, Fujiwara T, Maruo T, Itoh Y, Miyata M, Sakakibara S, Miyazaki N, Murata K, Yamaguchi Y, Haruta T, Nishioka H, Motojima Y, Komura M, Kimura K, Mandai K, Takai Y, Mizoguchi A.
  • Journal Title: J Comp Neurol Volume: - Issue: 12 Pages: 2719-2734
  • DOI: 10.1002/cne.24238
  • Peer Reviewed
• [Journal Article] Roles of afadin in functional differentiations of hippocampal mossy fiber synapse (2017)
  • Author(s): Geng Xiaoqi、Maruo Tomohiko、Mandai Kenji、Supriyanto Irwan、Miyata Muneaki、Sakakibara Shotaro、Mizoguchi Akira、Takai Yoshimi、Mori Masahiro
  • Journal Title: Genes to Cells Volume: 22 Issue: 8 Pages: 715-722
  • DOI: 10.1111/gtc.12508
  • Peer Reviewed
• [Journal Article] NGL-3-induced presynaptic differentiation of hippocampal neurons in an afadin-dependent, nectin-1-independent manner (2017)
  • Author(s): Maruo Tomohiko、Mandai Kenji、Miyata Muneaki、Sakakibara Shotaro、Wang Shujie、Sai Kousyoku、Itoh Yu、Kaito Aika、Fujiwara Takeshi、Mizoguchi Akira、Takai Yoshimi
  • Journal Title: Genes to Cells Volume: 22 Issue: 8 Pages: 742-755
  • DOI: 10.1111/gtc.12510
  • Peer Reviewed
• [Journal Article] Roles of afadin in the formation of the cellular architecture of the mouse hippocampus and dentate gyrus. (2017)
  • Author(s): Miyata M, Maruo T, Kaito A, Wang S, Yamamoto H, Fujiwara T, Mizoguchi A, Mandai K, Takai Y
  • Journal Title: Mol Cell Neurosci Volume: 79 Pages: 34-44
  • DOI: 10.1016/j.mcn.2016.12.007
  • Peer Reviewed
• [Journal Article] Aging-dependent expression of synapse-related proteins in the mouse brain. (2017)
  • Author(s): Shiotani, H., Maruo, T., Sakakibara, S., Miyata, M., Mandai, K., Mochizuki, H., Takai, Y.
  • Journal Title: Genes to Cells Volume: 印刷中 Issue: 5 Pages: 472-484
  • DOI: 10.1111/gtc.12489
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Localization of nectin-2δ at perivascular astrocytic endfoot processes and degeneration of astrocytes and neurons in nectin-2 knockout mouse brain. (2016)
  • Author(s): Miyata M, Mandai K, Maruo T, Sato J, Shiotani H, Kaito A, Itoh Y, Wang S, Fujiwara T, Mizoguchi A, Takai Y, Rikitake Y
  • Journal Title: Brain Res Volume: 1649 Pages: 90-101
  • DOI: 10.1016/j.brainres.2016.08.023
  • Peer Reviewed
• [Presentation] 海馬神経細胞のシナプス前部の分子的および機能的な分化におけるアファディンの関与 (2017)
  • Author(s): 丸尾 知彦、萬代 研二、宮田 宗明、榊原 正太郎、王 淑杰、崔 煌植、伊藤 優、垣内 愛加、藤原 武志、耿 瀟奇、イルワン スプリヤント、溝口 明、森 正弘、高井 義美
  • Organizer: 第40回日本神経科学大会
• [Presentation] 脳におけるネクチン－２の局在と機能 (2017)
  • Author(s): 宮田 宗明、萬代 研二、丸尾 知彦、佐藤 淳哉、塩谷 元、垣内 愛加、伊藤 優、王 淑杰、藤原 武志、溝口 明、高井 義美、力武 良行
  • Organizer: 第40回日本神経科学大会
• [Presentation] マウス網膜におけるNectin-1を介したSelf-to-Self新規接着機構の解析 (2017)
  • Author(s): 王 淑杰、垣内 愛加 、崔 煌植、萬代 研二、丸尾 知彦、高井 義美、溝口 明
  • Organizer: 第40回日本神経科学大会
• [Presentation] 海馬苔状線維シナプス分化における２つのアファディンスプライスバリアントの役割. (2016)
  • Author(s): 丸尾 知彦, 萬代 研二, 榊原 正太郎, 伊藤 優, 藤原 武志, 王 淑杰, 崔 煌植, 垣内 愛加, 耿 瀟奇, 森 正弘, 溝口 明, 高井 義美.
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-07-20
• [Presentation] 海馬発生におけるアファディンの役割. (2016)
  • Author(s): 宮田 宗明, 丸尾 知彦, 山本 昆明, 垣内 愛加, 王 淑杰, 藤原 武志, 溝口 明, 萬代 研二, 高井 義美.
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-07-20
• [Presentation] ネクチン-2αとマウス手綱核. (2016)
  • Author(s): 塩谷 元, 萬代 研二, 宮田 宗明, 丸尾 知彦, 垣内 愛加, 王 淑杰, 藤原 武志, 溝口 明, 望月 秀樹, 高井 義美.
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-07-20