Regulation of gamma-secretase activity

• Project/Area Number: 19680019
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Doshisha University
• Principal Investigator: FUNAMOTO Satoru Doshisha University, 生命医科学部, 准教授 (10345043)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥24,050,000 (Direct Cost: ¥18,500,000、Indirect Cost: ¥5,550,000); Fiscal Year 2009: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2008: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2007: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
• Keywords: アルツハイマー病 / アミロイドβタンパク質 / ガンマセクレターゼ / プレセニリン / ホスフォイノシチド / Aβ / PIP2 / Ass / ガンマセクレター

Research Abstract

γ-Secretase is an aspartic protease to hydrolyze type I transmembrane protein in hydrophobic environment of lipid bilayer. In this study, we analyzed effects of phosphoinositides on γ-secretase activity. We found that phosphoinositides inhibitedγ-secretase activity in the CHAPSO-solubilized assay system and detergent insoluble fraction, in dose dependent manner.

Research Products

• [Journal Article] γ-Secretase: Successive tripeptide and tetrapeptide release from the transmembrane domain of (R)-carboxyl terminal fragment. (2009)
  • Author(s): Mako Takami, Yu Nagashima, Yoshihisa Sano, Seiko Ishihara, Maho Morishima-Kawashima, Satoru Funamoto, Yasuo Ihara
  • Journal Title: J. Neurosci. 29 Pages: 13042-13052
  • Peer Reviewed
• [Journal Article] gamma-Secretase : Successive tripeptide and tetrapeptide release from the transmembrane domain of βCTF (2009)
  • Author(s): Takami et al.
  • Journal Title: J.Neurosci. 29 Pages: 13042-13052
  • Peer Reviewed
• [Journal Article] Phosphoinositides suppressγ-secretase in both the detergent-soluble and insoluble states. (2008)
  • Author(s): Satoko Osawa, Satoru Funamoto (corresponding author), Mika Nobuhara, Satoko Wada-Kakuda, Masafumi Shimojo, Sosuke Yagishita, Yasuo Ihara
  • Journal Title: J. Biol. Chem. 283 Pages: 19283-19292
  • Peer Reviewed
• [Journal Article] Enzymatic Characteristics of I213T Mutant Presenilin-1/γ-Secretase in Cell Models and Knock-in Mouse Brains FAMILIAL ALZHEIMER DISEASE-LINKED MUTATION IMPAIRSγ-SITE CLEAVAGE OF AMYLOID PRECURSOR PROTEIN C-TERMINAL FRAGMENTβ. (2008)
  • Author(s): Masafumi Shimojo, Naruhiko Sahara, Tatsuya Mizoroki, Satoru Funamoto, Maho Morishima -Kawashima, Takashi Kudo, Masatoshi Takeda, Yasuo Ihara, Hiroshi Ichinose, Akihiko Takashima.
  • Journal Title: J. Biol Chem. 283 Pages: 16488-16496
  • Peer Reviewed
• [Journal Article] Phosphoinositides suppress γ-secretase in both the detergent-soluble and insnbible states (2008)
  • Author(s): Osawa, et.al.
  • Journal Title: The Journal of Biological Chemistry 283 Pages: 19823-19292
  • Peer Reviewed
• [Journal Article] Enzymatic Characteristics of I213T Mutant Presenilin-1/γ-Secretase in Cell Models and Knock-in Mouse Brains FAMILIAL ALZHEIMER DISE ASE-LINKED MUTATION IMPAIRS γ-SITE CLEAVAGE OF AMYLOID PRECURSOR PROTEIN C-TERMINAL FRAGMENT ss (2008)
  • Author(s): Shimojo, et.al.
  • Journal Title: The Journal of Biological Chemistry 283 Pages: 16488-16496
  • Peer Reviewed
• [Journal Article] Active gamma-secretase complexes contain only one of each component. (2007)
  • Author(s): Toru Sato, Thekla S. Diehl, Saravanakumar Narayanan, Satoru Funamoto, Yasuo Ihara, Bart De Strooper, Harald Steiner, Christian Haass, Michael S. Wolfe.
  • Journal Title: J. Biol Chem. 282 Pages: 33985-33993
  • Peer Reviewed
• [Journal Article] Active gamma-secretase complexes contain only one of each component (2007)
  • Author(s): Sato, et. al.
  • Journal Title: Journal of Biological Chemistry 282 Pages: 33985-33993
  • Peer Reviewed
• [Presentation] アミロイドβタンパク質産生機序-トリペプチド仮説の検証- (2009)
  • Author(s): 舟本聡
  • Organizer: 第82回日本生化学会大会シンポジウム
  • Place of Presentation: 神戸市、兵庫県、日本
  • Year and Date: 2009-10-23
• [Presentation] アミロイドβタンパク質産生機序 -トリペプチド仮説の検証- (2009)
  • Author(s): 舟本聡
  • Organizer: 第82回日本生化学会大会シンポジウム
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • Year and Date: 2009-10-23
• [Presentation] γセクレターゼ活性におけるホスフォイノシチドの影響 (2007)
  • Author(s): 舟本聡
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜市、神奈川、日本
• [Presentation] Effects of phosphoinositides onγ-secretase activity in detergent soluble/insoluble states (2007)
  • Author(s): 舟本聡
  • Organizer: Society for Neuroscience meeting 2007
  • Place of Presentation: San Diego, CA USA
• [Presentation] Effects of phosphoinositides onγ-secretase activity in detergent soluble/insoluble states (2007)
  • Author(s): 舟本聡
  • Organizer: 第26回日本認知症学会学術集会
  • Place of Presentation: 大阪市、大阪、日本
• [Presentation] Effects of phosphoinositides on γ-secretase activity in detergent soluble/insoluble states (2007)
  • Author(s): Osawa, et. al.
  • Organizer: Society for Neuroscience meeting 2007
  • Place of Presentation: San Diego, CA USA
• [Presentation] Effects of phosphoinositides on γ-secretase activity in detergent soluble/insoluble states (2007)
  • Author(s): 大沢, ら、他4名
  • Organizer: 第26回日本認知症学会学術集会
  • Place of Presentation: 大阪市、大阪、日本
• [Presentation] γセクレターゼ活性におけるホスフォイノシチドの影響 (2007)
  • Author(s): 大沢, ら、他4名
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会 合同大会
  • Place of Presentation: 横浜市、神奈川、日本
• [Remarks]
  • URL: http://biomedical.doshisha.ac.jp/staff/index.html