COPII vesicle formation and the membrane trafficking in Alzheimer's disease.

• Project/Area Number: 19770101
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: The University of Tokyo
• Principal Investigator: FUTAI Eugene The University of Tokyo, 大学院・農学研究科, 准教授 (90447459)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥3,790,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2007: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: 膜輸送と輸送蛋白質 / アルツハイマー病 / 酵母 / γセクレターゼ / γ-セクレターゼ / 小胞輸送

Research Abstract

We identified a novel function of Sec16 in the generation of COPII vesicles from synthetic liposomes. In the presence of Sec16, nucleotide hydrolysis by Sar1 was inhibited, enabling Sar1 atabilization on the membranes. To clarify the importance of the membrane trafficking in Alzheimer's disease, we introducedγsecretase, a multisubunit membrane protein complex, and the amyloid precursor in yeast and established an in vitroγsecretase assay system and a screening system based on yeast growth.

Research Products

• [Journal Article] beta-secretase inhibi tor potency is decreased by aberrant bet a-cleavage location of the "Swedish mut ant" amyloid precursor protein. (2010)
  • Author(s): Yamakawa, H., Yagishita, S., Futai, E., Ishiura, S.
  • Journal Title: J.BiolJ.Biol.Chem. Vol.285 Pages: 1634-1642
  • Peer Reviewed
• [Journal Article] Reduction of amyloid beta-peptide accumulation in Tg2576 transgenic mice by oral vaccination. (2010)
  • Author(s): Ishii-Katsuno R., Nakajima, A., Katsuno, T., Nojima, J., Futai, E., Sasagawa, N., Yoshida, T., Watanabe, Y., Ishiura, S.
  • Journal Title: Biochem. Biophys. Res.Commun. Vol.399 Pages: 593-599
  • Peer Reviewed
• [Journal Article] beta-secretase inhibitor potency is decreased by aberrant beta-cleavage location of the "Swedish mutant" amyloid precursor protein. (2010)
  • Author(s): Yamakawa, H., Yagishita, S., Futai, E., Ishiura, S.
  • Journal Title: Journal of Biological Chemistry Volume: 285 Pages: 1634-1642
  • Peer Reviewed
• [Journal Article] Nicastrin is dispensable for γ secretase protease activity in the presence of specific presenilin mutations. (2009)
  • Author(s): Futai, E., Yagishita, S. Ishiura, S.
  • Journal Title: J.Biol.Chem. Vol.284 Pages: 13013-13022
  • Peer Reviewed
• [Journal Article] Nicastrin is dispensable for γ secretase protease activity in the presence of specific presenilin mutations. (2009)
  • Author(s): Futai, E., Yagishita, S., Ishiura, S.
  • Journal Title: Journal of Biological Chemistry Volume: 284 Pages: 13013-13022
  • Peer Reviewed
• [Journal Article] Biochemical analysis of oligomerization of expanded polyalanine repeat proteins. (2009)
  • Author(s): Nojima, J., Oma, Y., Futai, E., Sasagawa, N., Kuroda, R., Turk, B., Ishiura, S.
  • Journal Title: Journal of Neuroscience Research Volume: 87 Pages: 2290-2296
  • Peer Reviewed
• [Journal Article] Polyalanine tracts directly induce the release of cytochrome c, independently of the mitochondrial permeability pore, leading to apoptosis. (2009)
  • Author(s): Toriumi, K., Oma, Y., Mimoto, A., Futai, E., Sasagawa, N., Turk, B., Ishiura, S.
  • Journal Title: Genes to Cells Volume: 14 Pages: 751-757
  • Peer Reviewed
• [Journal Article] Nicastrin is dispensable for γ-secretase protease activity in the presence of specific presenilin mutations (2009)
  • Author(s): Futai, E., Yagishita, S., and Ishiura, S.
  • Journal Title: Journal of Biological Chemistry (advanced on line nublification)
  • Peer Reviewed
• [Journal Article] In vitro reconstitution of γ-secretase activity using yeast microsomes. (2008)
  • Author(s): Yagishita, S., Futai, E., Ishiura, S.
  • Journal Title: Biochem. Biophys. Res.Commun. Vol.377 Pages: 141-145
  • Peer Reviewed
• [Journal Article] Inhibition by KMI-574 leads to dislocalization of BACE1 from lipid rafts. (2008)
  • Author(s): Ebina, M., Futai, E., Tanabe, C., Sasagawa, N., Kiso, Y., Ishiura, S.
  • Journal Title: J.Neurosci. Res. Vol.87 Pages: 360-368
  • Peer Reviewed
• [Journal Article] 1,3-Capryloyl-2-arachidonoyl glycerol activates alpha-secretase activity and suppresses Abeta40 secretion in A172 cells. (2008)
  • Author(s): Tanabe, C., Ebina, M., Asai, M., Futai, E., Sasagawa, N., Katano, K., Fukami, H., Ishiura, S.
  • Journal Title: Neuroscience Letter Vol.450 Pages: 324-326
  • Peer Reviewed
• [Journal Article] Csk-homologous kinase interacts with SHPS-1 and enhances neurite outgrowth of PC12 cells. (2008)
  • Author(s): Mitsuhashi H, Futai E, Sasagawa N, Hayashi Y, Nishino I, Ishiura S.
  • Journal Title: J.Neurochem. Vol.105 Pages: 101-112
  • Peer Reviewed
• [Journal Article] In vitro reconstitution of γ-secretase activity using yeast microsomes (2008)
  • Author(s): Yagishita, S., Futai, E., and Ishiura, S.
  • Journal Title: Biochem. Biophys. Res. Commun 377 Pages: 141-145
  • Peer Reviewed
• [Journal Article] Inhibition by KMI-574 leads to dislocalization of BACEI from lipid rafts (2008)
  • Author(s): Ebina, M., Futai, E., Tanabe, C., Sasagawa, N., Kiso, Y., and Ishiura, S.
  • Journal Title: Journal of Neuroscience Research 87 Pages: 360-368
  • Peer Reviewed
• [Journal Article] Dysbindin-I, a schizophrenia-related protein, functionally interacts with the DNA-dependent protein kinase complex in an isoform-dependent manner (2008)
  • Author(s): Oyama, S., Yamakawa, H., Sasagawa, N., Hosoi, Y., Futai, E., and Ishiura S.
  • Journal Title: PLoS ONE 4
  • Peer Reviewed
• [Journal Article] 1, 3-Capryloyl-2-arachidonoyl glycerol activates alpha-secretase activity and suppresses Abeta40 secretion in A172 cells (2008)
  • Author(s): Tanabe, C., Ebina, M., Asai, M., Futai, E., Sasagawa, N., Katano, K., Fukami, H., and Ishiura, S.
  • Journal Title: Neuroscience Letter 450 Pages: 324-326
  • Peer Reviewed
• [Journal Article] MBNL1 associates with YB-1 in cytoplasmic stress granules (2008)
  • Author(s): Onishi, H., Kino, Y., Morita, T., Futai, E., Sasagawa, N., and Ishiura, S.
  • Journal Title: Journal of Neuroscience Research 86 Pages: 1994-2002
  • Peer Reviewed
• [Journal Article] Expression of polyalanine stretches induces mitochondrial dysfunction (2008)
  • Author(s): Toriumi, K., Oma, Y., Kino, Y., Futai, E., Sasagawa, N., and Ishiura, S.
  • Journal Title: Journal of Neuroscience Research 86 Pages: 1529-1537
  • Peer Reviewed
• [Journal Article] Csk-homologous kinase interacts with SHPS-1 and enhances neurite outgrowth of PC12 cells. (2008)
  • Author(s): Mitsuhashi H, Futai E, Sasagawa N, Hayashi Y, Nishino I, Ishiura S.
  • Journal Title: Journal of Neurochemistry 105 Pages: 101-112
  • Peer Reviewed
• [Journal Article] Expression of polyalanine stretches induces mitochondrial dysfunction. (2008)
  • Author(s): Toriumi K, Oma Y, Kino Y, Futai E, Sasagawa N, Ishiura S.
  • Journal Title: Journal of Neuroscience Research Early View on line
  • Peer Reviewed
• [Journal Article] MBNL1 associates with YB-1 in cytoplasmic stress granules. (2008)
  • Author(s): Onishi H, Kino Y, Morita T, Futai E, Sasagawa N, Ishiura S.
  • Journal Title: Journal of Neuroscience Research Early View on line
  • Peer Reviewed
• [Presentation] 酵母γセクレターゼ再構成系を用いたpresenilin変異体の解析 (2010)
  • Author(s): 二井勇人、柳下聡一、石浦章一
  • Organizer: 酵母遺伝学フォーラム
  • Place of Presentation: ならまちセンター(奈良)
  • Year and Date: 2010-09-09
• [Presentation] 酵母でのγセクレターゼ再構成系を用いたpresenilin変異体の解析(Nicastrin is dispensable for gamma-secretase activity in the presence of specific presenilin mutations) (2009)
  • Author(s): 二井勇人、柳下聡一、石浦章一
  • Organizer: 第82回日本生化学大会
  • Place of Presentation: 神戸国際会議場(兵庫)
  • Year and Date: 2009-10-23
• [Presentation] 酵母でのγセクレターゼ再構成系を用いたpresenilin変異体の解析 (2009)
  • Author(s): 二井勇人
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2009-10-23
• [Presentation] アルツハイマー病治療を目指した○!Cセクレターゼ活性評価系の開発 (2009)
  • Author(s): 二井勇人、柳下聡一、石浦章一
  • Organizer: 第14回日本病態プロテアーゼ学会
  • Place of Presentation: 千里ライフサイエンスセンター(大阪)
  • Year and Date: 2009-08-21
• [Presentation] Nicastrin is dispensable for protease activity of γ -secretase. (2008)
  • Author(s): Futai, E., Yagishita, S., Ishiura, S.
  • Organizer: Society for Neuroscience 2008(北米神経科学会2008)
  • Place of Presentation: ワシントンD.C.(米国)
  • Year and Date: 2008-11-17
• [Presentation] Recnstitution of γ-secretase activity using yeast microsome fraction. (2008)
  • Author(s): Yagishita, S., Futai, E., Ishiura, S.
  • Organizer: Society for Neuroscience 2008(北米神経科学会2008)
  • Place of Presentation: ワシントンD.C.(米国)
  • Year and Date: 2008-11-17
• [Presentation] Nicastrin is dispensable for protease activity of the γ-secretase (2008)
  • Author(s): Futai, E., Yagishita, S., and Ishiura, S.
  • Organizer: Society for Neurosciece(北米神経科学会2008)
  • Place of Presentation: 米国ワシントンD.C
  • Year and Date: 2008-11-17
• [Presentation] Sec16 inhibits GAP activity of COPII coat on synthetic liposomes. (2007)
  • Author(s): Futai, E., Hamamoto, S., Schekman, R.
  • Organizer: 第80回日本生化学会大会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2007-12-13
• [Presentation] Sec16 inhibits GAP activity of the COPII coat on synthetic liposomes (2007)
  • Author(s): Futai, E., Hamamoto, S., and Schek man, R.
  • Organizer: 第80回日本生化学会大会
  • Place of Presentation: 神奈川
• [Book] 脳21(膜結合型メタロプロテアーゼ(MMP、ADAM)ファミリー)13巻(No.1) (2010)
  • Author(s): 二井勇人、石浦章一
  • Publisher: 金芳堂社
• [Book] 生物の科学『遺伝』(家族性自閉症の遺伝子変異)61巻(No.3) (2007)
  • Author(s): 石浦章一、山川英訓、二井勇人
  • Publisher: 裳華房社
• [Remarks] ホームページ等