Regulation of gamma-secretase activity

2009 Fiscal Year Final Research Report

• 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
• 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

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] 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] 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
• [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] 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
  • Year and Date: 20071211-20071215
• [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
  • Year and Date: 20071103-20071107
• [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
  • Year and Date: 20071017-20071018
• [Remarks]
  • URL: http://biomedical.doshisha.ac.jp/staff/index.html