Establishment of a new paradigm in the phosphoinositide research

• Project/Area Number: 21200075
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry; Biological pharmacy
• Research Institution: Akita University
• Principal Investigator: SASAKI Junko 秋田大学, 大学院・医学系研究科, 講師 (30333371)
• Co-Investigator(Kenkyū-buntansha): INOUE Takao 国立医薬品食品研究所, 主任研究官 (50361605)
• Co-Investigator(Renkei-kenkyūsha): TAGUCHI Ryo 中部大学, 生命健康科学部, 教授 (20080210) ; KOFUJI Satoshi 秋田大学, 大学院・医学系研究科, 助教 (00508153) ; TAKASUGA Shunsuke 秋田大学, 大学院・医学系研究科, 助教 (90375262) ; EGUCHI Satoshi 秋田大学, 大学院・医学系研究科, 助教 (70457117)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥28,730,000 (Direct Cost: ¥22,100,000、Indirect Cost: ¥6,630,000); Fiscal Year 2011: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000); Fiscal Year 2010: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000); Fiscal Year 2009: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
• Keywords: 分子病態学 / シグナル伝達 / 脂質 / 細胞・組織

Research Abstract

There are two isozymes (L-PIPase and P-PIPase) which dephosphorylate PI(3,4)P2. However the functions of L-PIPase and P-PIPase are unclear. In this study we showed that L-PIPase suppresses neuronal cell death after brain ischemia while P-PIPase contributes to malignant progression. We also found that each enzyme has different activities against several PI(3,4)P2 species. It is suggested that the different functions between L-PIPase and P-PIPase might be caused by the substrate specificity.

Research Products

• [Journal Article] Blockade of class IB phosphoinositide-3 kinase ameliorates obesity-induced inflammation and insulin resistance (2011)
  • Author(s): Kobayashi N, Ueki K, Okazaki Y, Iwane A, Kubota N, Ohsugi M, Awazawa M, Kobayashi M, Sasako T, Kaneko K, Suzuki M, Nishikawa Y, Hara K, Yoshimura K, Koshima I, Goyama s, Murakami K, Sasaki J, Nagai R, Kurokawa M, Sasaki T, Kadowaki T
  • Journal Title: Proc.Natl.Acad.Sci.USA Volume: 108 Issue: 14 Pages: 5753-5758
  • DOI: 10.1073/pnas.1016430108
  • Peer Reviewed
• [Journal Article] Intracellular phosphatidylserine is essential for retrograde membrane traffic through endosomes (2011)
  • Author(s): Uchida, Y., Hasegawa, J., et al(22名中4番目)
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 108 Issue: 38 Pages: 15846-15851
  • DOI: 10.1073/pnas.1109101108
  • Peer Reviewed
• [Journal Article] The Pas-PI3K signaling pathway is involved in clathrin-independent endocytosis and the internalization of influenza viruses (2011)
  • Author(s): Fujioka, Y., Tsuda, M., et al(7名中4番目)
  • Journal Title: PLoS One Volume: 6 Issue: 1 Pages: e16324-e16324
  • DOI: 10.1371/journal.pone.0016324
  • Peer Reviewed
• [Journal Article] Epimorphin protects hepatocytes from oxidative stress by inhibiting mitochondrial injury (2011)
  • Author(s): Kinoshita, N., Horie, Y., et al(11名中8番目)
  • Journal Title: J. Gastroenterol Hepatol. Volume: 26 Issue: 1 Pages: 201-206
  • DOI: 10.1111/j.1440-1746.2010.06327.x
  • Peer Reviewed
• [Journal Article] Phosphoinositide 3-kinaseγ controls the intracellular localization of CpG to limit DNA-PKcs-dependent IL-10 production in macrophages (2011)
  • Author(s): Hazeki, K., Kametani, Y., et al, (11名中7番目)
  • Journal Title: PLoS One. Volume: 6 Issue: 10 Pages: e26836-e26836
  • DOI: 10.1371/journal.pone.0026836
  • Peer Reviewed
• [Journal Article] The Ras-PI3K signaling pathway is involved in clathrin-independent endocytosis and the internalization of influenza viruses. (2011)
  • Author(s): Fujioka, Y.
  • Journal Title: PLoS One Volume: 6
  • Peer Reviewed
• [Journal Article] The PI(3,4)P2 phosphatase INPP4A is a suppressor of excitotoxic Neuronal Death (2010)
  • Author(s): Sasaki, J., Kofuji, S., et al(20名中1番目, 2番目, 9番目, 10番目)
  • Journal Title: Nature Volume: 465 Issue: 7297 Pages: 497-501
  • DOI: 10.1038/nature09023
  • Peer Reviewed
• [Journal Article] Intracellular PLA1 and acyltransferase, which are involved in C. elegans stem cell divisions, determine the sn-1 fatty acyl chain of phosphatidylinositol (2010)
  • Author(s): Imae, R., Inoue, T., et al(8名中2番目)
  • Journal Title: Mol. Biol. Cell Volume: 21 Issue: 18 Pages: 3114-3124
  • DOI: 10.1091/mbc.e10-03-0195
  • Peer Reviewed
• [Journal Article] Phosphatidylinositol-4-pho5-kinases and phosphatidylinositol 4,5-bisphosphate synthesis in the brain (2010)
  • Author(s): Volpicelli-Daley, L., A., Lucast, L., et al(9名中5番目)
  • Journal Title: J. Biol. Chem. Volume: 285 Issue: 37 Pages: 28708-28714
  • DOI: 10.1074/jbc.m110.132191
  • Peer Reviewed
• [Journal Article] Decrease in membrane phospholipid unsaturation induces unfolded protein response (2010)
  • Author(s): Ariyama, H., Kono, N., et al(5名中4番目)
  • Journal Title: J. Biol. Chem. Volume: 285 Issue: 29 Pages: 22027-22035
  • DOI: 10.1074/jbc.m110.126870
  • Peer Reviewed
• [Journal Article] Multivesicular body formation requires OSBP-related proteins and cholesterol (2010)
  • Author(s): Kobuna, H., Inoue, T., et al(7名中2番目)
  • Journal Title: PLoS Genetics Volume: 6 Issue: 8 Pages: e1001055-e1001055
  • DOI: 10.1371/journal.pgen.1001055
  • Peer Reviewed
• [Journal Article] LC3, a microtubule-associated protein1A/B light chain3, is involved in cytoplasmic lipid droplet formation (2010)
  • Author(s): Shibata, M., Yoshimura, K., et al(11名中6番目)
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 393 Issue: 2 Pages: 274-279
  • DOI: 10.1016/j.bbrc.2010.01.121
  • Peer Reviewed
• [Journal Article] Two very long chain fatty acid acyl-CoA synthetase genes, acs-20 and acs-22, have roles in the cuticle surface barrier in Caenorhabditis elegans (2010)
  • Author(s): Kage-Nakadai, E., Kobuna, H., et al(7名中5番目)
  • Journal Title: PLoS ONE Volume: 5 Issue: 1 Pages: e8857-e8857
  • DOI: 10.1371/journal.pone.0008857
  • Peer Reviewed
• [Journal Article] The PI(3,4)P2 phosphatase INPP4A is a suppressor of excitotoxic Neuronal Death. (2010)
  • Author(s): Sasaki, J.
  • Journal Title: Nature Volume: 465 Pages: 497-501
  • Peer Reviewed
• [Journal Article] Phosphatidylinositol-4-phosphate 5-kinases and phosphatidylinositol 4,5-bisphosphate synthesis in the brain. (2010)
  • Author(s): Volpicelli-Daley, L.A.
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 28708-28714
  • Peer Reviewed
• [Journal Article] Sex difference in the liver of hepatocyte-specific Pten-deficient mice : A model of nonalcoholic steatohepatitis (2009)
  • Author(s): Anezaki, Y., Ohshima, S., et al(14名中10番目)
  • Journal Title: Hepatol. Res. Volume: 39 Issue: 6 Pages: 609-618
  • DOI: 10.1111/j.1872-034x.2009.00494.x
  • Peer Reviewed
• [Journal Article] Eicosapentaenoic acid ameliorates steatohepatitis and hepatocellular carcinoma in hepatocyte-specific Pten-deficient mice (2009)
  • Author(s): Ishii, H., Horie, Y., et al(14名中10番目)
  • Journal Title: J. Hepatol. Volume: 50 Issue: 3 Pages: 562-571
  • DOI: 10.1016/j.jhep.2008.10.031
  • Peer Reviewed
• [Journal Article] Mammalian phosphoinositide kinases and phosphatases (2009)
  • Author(s): Sasaki, T., Takasuga, S., Sasaki, J., Kofuji, S., Eguchi, S., Yamazaki, M. & Suzuki, A.
  • Journal Title: Prog. Lipid Res. Volume: 48 Issue: 6 Pages: 307-343
  • DOI: 10.1016/j.plipres.2009.06.001
• [Journal Article] Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis (2009)
  • Author(s): Fukui Y(著者16名、16番目)
  • Journal Title: Science Volume: 324 Issue: 5925 Pages: 384-387
  • DOI: 10.1126/science.1170179
  • Peer Reviewed
• [Journal Article] Functional analysis of GS28, an intra-Golgi SNARE, in C. elegans (2009)
  • Author(s): Maekawa, M., Inoue, T., et al(7名中2番目)
  • Journal Title: Genes to Cells Volume: 14 Issue: 8 Pages: 1003-1013
  • DOI: 10.1111/j.1365-2443.2009.01325.x
  • Peer Reviewed
• [Journal Article] Normal formation of a subset of intestinal granules in Caenorhabditis elegans requires ABC transporters HAF-4 and HAF-9, which are highly homologous to human lysosomal peptide transporter TAPL (TAP-like) (2009)
  • Author(s): Kawai, H., Tanji, T., et al(13名中6番目)
  • Journal Title: Mol. Biol. Cell Volume: 20 Issue: 12 Pages: 2979-2990
  • DOI: 10.1091/mbc.e08-09-0912
  • Peer Reviewed
• [Journal Article] Nematode homologue of PQBP1, a mental retardation causative gene, is involved in lipid metabolism (2009)
  • Author(s): Takahashi, K., Yoshina, S., et al(9名中5番目)
  • Journal Title: PLoS ONE Volume: 4 Issue: 1 Pages: e4104-e4104
  • DOI: 10.1371/journal.pone.0004104
  • Peer Reviewed
• [Journal Article] Mammalian phosphoinositide kinases and phosphatases (2009)
  • Author(s): Sasaki, T.
  • Journal Title: Prog.Lipid Res. 48 Pages: 307-343
  • Peer Reviewed
• [Journal Article] Sex difference in the liver of hepatocyte-specific Pten-deficient mice : A model of nonalcoholic steatohepatitis (2009)
  • Author(s): Anezaki, Y.
  • Journal Title: Hepatol.Res. 39 Pages: 609-618
  • Peer Reviewed
• [Journal Article] Eicosapentaenoic acid ameliorates steatohepatitis and hepatocellular carcinoma in hepatocyte-specific Pten-deficient mice (2009)
  • Author(s): Ishii, H.
  • Journal Title: J.Hepatol. 50 Pages: 562-571
  • Peer Reviewed
• [Presentation] The lipid phosphatase INPP4A prevents striatal neurons from excitotoxic death (2010)
  • Author(s): 佐々木純子
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] Identification of enzymes involved in fatty acid remodeling of phosphatidylinositol (2010)
  • Author(s): 井上貴雄
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] The lipid phosphatase INPP4A prevents striatal neurons from excitotoxic death (2010)
  • Author(s): 佐々木純子
  • Organizer: BMB2010
  • Place of Presentation: ポートピアホテル(兵庫県)
  • Year and Date: 2010-12-08
• [Presentation] リン脂質アシルトランスフェラーゼの包括的解析 (2009)
  • Author(s): 井上貴雄
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-24
• [Book] ホスファチジルイノシトール3,4-二リン酸脱リン酸化酵素INPP4Aは、興奮毒性による神経細胞死の抑制因子である、細胞工学29(9) (2010)
  • Author(s): 佐々木純子、浅沼研、佐々木雄彦
  • Publisher: 学研メディカル秀潤社
• [Book] ホスホイノシタイドホスファターゼの異常と病態、実験医学28(20) (2010)
  • Author(s): 佐々木純子、小藤智史、佐々木雄彦
  • Publisher: 羊土社
• [Book] ホスファチシルイノシトールの脂肪酸組成を規定する酵素群の同定、実験医学28(20) (2010)
  • Author(s): 井上 貴雄、新井 洋由
  • Publisher: 羊土社
• [Remarks]
  • URL: http://www.med.akita-u.ac.jp/~bisei/
• [Remarks]
  • URL: http://www.med.akita-u.ac.jp/~bisei/
• [Remarks]
  • URL: http://www.med.akita-u.ac.jp/~bisei/
• [Remarks]
  • URL: http://www.med.akita-u.ae.jp/~bisei/