Conformational change of X11L and its physiological functions

• Project/Area Number: 23790069
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Hokkaido University
• Principal Investigator: SAITO Yuhki 北海道大学, 大学院・薬学研究院, 助教 (70548180)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: アルツハイマー病 / X11L / リン酸化 / APP / X１１ / Alzheimer's Disease / Aβ / X11s

Research Abstract

The purpose of this research is to reveal the mechanism of AD pathogenesis. X11-like (X11L) protein has been identified as a suppressor of AD pathogenesis. We revealed in this project that the conformational change of X11L was correlated to the amount of Aβ generation and that its conformational change was regulated by the phosphorylation of calboxyl-terminal of X11L protein. Moreover, we identified a few candidate kinases of X11L protein.

Research Products

• [Journal Article] Hyperpolarization-activated cyclic nucleotide gated channels: a potential molecular link between epileptic seizures and Abeta generation in Alzheimer's disease (2012)
  • Author(s): Saito Y
  • Journal Title: Mol Neurodegener Volume: 7 Issue: 1 Pages: 50-50
  • DOI: 10.1186/1750-1326-7-50
  • Peer Reviewed
• [Journal Article] Constitutive Cleavage of the Single-pass Transmembrane Protein Alcadeinα Prevents Aberrant Peripheral Retention of Kinesin-1. (2012)
  • Author(s): Chiaki Maruta
  • Journal Title: PLoS One Volume: 7 Issue: 8 Pages: e43058-e43058
  • DOI: 10.1371/journal.pone.0043058
  • Peer Reviewed
• [Journal Article] Membrane-microdomain localization of amyloid β-precursor protein (APP) C-terminal fragments is regulated by phosphorylation of the cytoplasmic Thr668 residue (2012)
  • Author(s): Matsushima T
  • Journal Title: J Biol Chem Volume: 287 Issue: 23 Pages: 19715-19724
  • DOI: 10.1074/jbc.m111.334847
  • Peer Reviewed
• [Journal Article] Coordinated increase of y-secretase products in the plasma of some female Japanese sporadic Alzheimer's disease patients: quantitative analysis of p3-Alca with a new ELISA system (2011)
  • Author(s): Konno, et al.
  • Journal Title: Molecular Neurodegeneration Volume: 6 Issue: 1 Pages: 76-76
  • DOI: 10.1186/1750-1326-6-76
  • Peer Reviewed
• [Journal Article] Intracellular trafficking of the amyloid β-protein precursor (APP) regulated by novel function of X11-like (2011)
  • Author(s): Saito Y
  • Journal Title: PLoS One Volume: 6 Issue: 7 Pages: e22108-e22108
  • DOI: 10.1371/journal.pone.0022108
  • Peer Reviewed
• [Presentation] 神経細胞活動とアルツハイマー病 (2012)
  • Author(s): 齋藤有紀
  • Organizer: 第132年会日本薬学会
  • Place of Presentation: 北海道大学(北海道)[特別シンポジウムOS11-1]
  • Year and Date: 2012-03-31
• [Presentation] APP代謝・輸送制御を担うX11-like(X11L)の機能ドメイン (2012)
  • Author(s): 方家,齋藤有紀,鈴木利治
  • Organizer: 第132年回日本薬学会
  • Place of Presentation: 北海道大学(北海道)
  • Year and Date: 2012-03-29
• [Presentation] Involvement of X11/X11L in Alzheimer's-related beta-amyloid generation and epileptogenesis (2012)
  • Author(s): Kanada, Y., Saito, Y., Nishimura, M., Kimura, N. and Suzuki T
  • Organizer: Alzheimer's Association International Conference 2012
  • Place of Presentation: Vancourver Convention Center, Vancouver, British Columbia, Canada
• [Presentation] Membrane microdomain localization of APP C-terminal fragments regulated by the phosphorylation at cytoplasmic Thr668 residue (2012)
  • Author(s): Matsushima, T., Saito, Y., Nishimura, M., Kimura, N., Hata, S. and Suzuki T
  • Organizer: Alzheimer's Association International Conference 2012
  • Place of Presentation: Vancourver Convention Center, Vancouver, British Columbia, Canada
• [Presentation] Membrane microdomain localization of APP C-terminal fragments regulated by the phosphorylation at cytoplasmic Thr668 residue (2012)
  • Author(s): Takahide Matsushima
  • Organizer: Alzheimer's Association International Conference 2012
  • Place of Presentation: Vancourver Convention Center (Canada)
• [Presentation] Involvement of X11/X11L in Alzheimer's-related beta-amyloid generation and epileptogenesis (2012)
  • Author(s): Yoshihiro Kanada
  • Organizer: Alzheimer's Association International Conference 2012
  • Place of Presentation: Vancourver Convention Center (Canada)
• [Presentation] 神経細胞活動とアルツハイマー病 (2012)
  • Author(s): 齋藤有紀
  • Organizer: 第132年回 日本薬学会(招待講演)
  • Place of Presentation: 北海道大学（札幌市）
• [Presentation] APP代謝・輸送制御を担うX11-like (X11L)の機能ドメイン (2012)
  • Author(s): 方家, 齋藤有紀，鈴木利治
  • Organizer: 第132年回 日本薬学会
  • Place of Presentation: 北海道大学（札幌市）
• [Presentation] Intracellular Trafficking of the Amyloid ss-Protein Precursor Regulated by PDZ domains of X11-Like (2011)
  • Author(s): Yuhki Saito and Toshiharu Suzuki
  • Organizer: 51th The American society for cell biology annual meeting
  • Place of Presentation: The Colorado convention center, Denver (CO), USA
  • Year and Date: 2011-12-05
• [Presentation] Alcadeinαの欠損によりAPPのアミロイド産生的代謝は亢進する (2011)
  • Author(s): 山本融,後藤直也,齋藤有紀,羽田沙緒里,松崎文雄,鈴木利治
  • Organizer: 第34回日本神経科学大会Neuroscience2011
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-09-16
• [Presentation] X11-/-; X11L-/-マウスとアルツハイマー病モデルマウスで認められるHCNチャネル機能異常 (2011)
  • Author(s): 齋藤有紀,井上剛,鈴木利治
  • Organizer: 第34回日本神経科学大会Neuroscience2011
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-09-15
• [Presentation] APP metabolism in brain of alcadein α CTF transgenic mice (2011)
  • Author(s): Ayano Kimura, Norio Takei, Saori Hata, Yuhki Saito, Toshiharu Suzuki
  • Organizer: Alzheimer's Association International Conference 2011
  • Place of Presentation: Paris Porte de Versailles Convention and Exhibition Center, Paris, France
  • Year and Date: 2011-07-19
• [Presentation] Quantification of plasma p3-Alc α level with s ELISA systems] Alzheimer's Association International Conference 2011, Paris Porte de Versailles Convention and Exhibition Center (2011)
  • Author(s): Jia Fang, Tomoko Konno, Yuko Horikoshi-Sakuraba, Saori Hata, Yuhki Saito, Masahiro Maeda, Hiroyasu Akatsu, Toshiharu Suzuki.
  • Organizer: Paris
  • Place of Presentation: France
  • Year and Date: 2011-07-19
• [Presentation] Toshiharu Suzuki [Enhanced amyloidogenic processing of APP in Alcadein α-deficient mice] Alzheimer's Association International Conference 2011 (2011)
  • Author(s): Naoya Gotoh, Yuhki Saito, Saori Hata, Tohru Yamamoto
  • Organizer: Paris Porte de Versailles Convention and Exhibition Center
  • Place of Presentation: Paris, France
  • Year and Date: 2011-07-19
• [Presentation] Toshiharu Suzuki [Malfunction of HCN channels in X11/X11L doubly deficient mice] Alzheimer's Association International Conference 2011 (2011)
  • Author(s): Yuhki Saito, Tsuyoshi Inoue
  • Organizer: Paris Porte de Versailles Convention and Exhibition Center
  • Place of Presentation: Paris, France
  • Year and Date: 2011-07-17
• [Presentation] Identification of a gene which controls abeta accumulation using APP Tg mice with mixed genetic background splicing variant specific effect of kinesin light chain 1 (KLC1) (2011)
  • Author(s): Mikiko Yokokoji, Morihara Takeshi, Noriyuki Hayashi, Masayasu Okochi, Toshiharu Suzuki, Yuhki Saito, Nobuyuki Kimura, Masatoshi Takeda, Hiroaki Kazui, Hiroyasu Akatsu, Akitaka Takamura, Taiichi Katayama, Naohiro Ito, Shinichi Tatsumi, Kiyoko Kato, Kanta Yanagida, Takashi Kodama, Shinji Tagami, Norihisa Tanaka, Takashi Kudo, Takashi Morihara
  • Organizer: Alzheimer's Association International Conference 2011, Paris Porte de Versailles Convention and Exhibition Center
  • Place of Presentation: Paris, France
  • Year and Date: 2011-07-17
• [Presentation] Intracellular Trafficking of the Amyloid β-Protein Precursor Regulated by PDZ domains of X11-Like (2011)
  • Author(s): Yuhki Saito, Toshiharu Suzuki
  • Organizer: 51th ASCB annual meeting
  • Place of Presentation: Colorado Convention Center (USA)
• [Presentation] Alcadeinαの欠損によりAPPのアミロイド産生的代謝は亢進する (2011)
  • Author(s): 山本融，後藤直也，齋藤有紀，羽田沙緒里，松崎文雄，鈴木利治
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] X11-/-; X11L-/-マウスとアルツハイマー病モデルマウスで認められるHCNチャネル機能異常 (2011)
  • Author(s): 齋藤有紀，井上剛，鈴木利治
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] APP metabolism in brain of alcadein α CTF transgenic mice (2011)
  • Author(s): Ayano Kimura, Norio Takei, Saori Hata, Yuhki Saito, Toshiharu Suzuki
  • Organizer: AAIC 2011
  • Place of Presentation: Porte de Versailles (France)
• [Presentation] Quantification of plasma p3-Alc α level with s ELISA systems (2011)
  • Author(s): Jia Fang, Tomoko Konno, Yuko Horikoshi-Sakuraba, Saori Hata, Yuhki Saito, Masahiro Maeda, Hiroyasu Akatsu, Toshiharu Suzuki.
  • Organizer: AAIC 2011
  • Place of Presentation: Porte de Versailles (France)
• [Presentation] Enhanced amyloidogenic processing of APP in Alcadein α-deficient mice (2011)
  • Author(s): Naoya Gotoh, Yuhki Saito, Saori Hata, Tohru Yamamoto, Toshiharu Suzuki
  • Organizer: AAIC 2011
  • Place of Presentation: Porte de Versailles (France)
• [Presentation] Malfunction of HCN channels in X11/X11L doubly deficient mice (2011)
  • Author(s): Yuhki Saito, Tsuyoshi Inoue, Toshiharu Suzuki
  • Organizer: AAIC 2011
  • Place of Presentation: Porte de Versailles (France)
• [Presentation] Identification of a gene which controls abeta accumulation using APP Tg mice with mixed genetic background splicing variant specific effect of kinesin light chain 1 (KLC1) (2011)
  • Author(s): Mikiko Yokokoji, Morihara Takeshi, Noriyuki Hayashi, Masayasu Okochi, Toshiharu Suzuki, Yuhki Saito, et al.
  • Organizer: AAIC 2011
  • Place of Presentation: Porte de Versailles (France)
• [Book] Understanding Alzheimer's Disease: Mechanism of Alzheimer amyloid ss-protein precursor localization to membrane lipid rafts. (2013)
  • Author(s): Yuhki Saito, Takahide Matsusgima, Toshiharu Suzuki.
  • Publisher: Edited by Inga Zerr
• [Book] Understanding Alzheimer's Disease: Mechanism of Alzheimer amyloid β-protein precursor localization to membrane lipid rafts (2013)
  • Author(s): Yuhki Saito
  • Total Pages: 25
  • Publisher: INTECH
• [Book] γセクレターゼ研究とAss産生を標的とした薬剤開発の現状-APPおよびAPP切断産物の機能(Functions of APP and APP derived-fragments) (2012)
  • Author(s): 齋藤有紀,鈴木利治 (Yuhki Saito, Toshiharu Suzuki)
  • Publisher: 日本認知症学会誌(Dementia Japan) 26
• [Book] Functions of APP and APP derived-fragments (2012)
  • Author(s): Yuhki Saito
  • Total Pages: 9
  • Publisher: Dementia Japan
• [Book] APPおよびAPP切断産物の機能 (2012)
  • Author(s): 齋藤有紀，鈴木利治
  • Publisher: 日本認知症学会誌 (Dementia Japan)
• [Remarks]
  • URL: http://www.pharm.hokudai.ac.jp/org/shinkei01.html