Physiological significance of phosphatidylinositol (PI) molecular species in PI signaling

• Project/Area Number: 20370045
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: The University of Tokyo
• Principal Investigator: ARAI Hiroyuki The University of Tokyo, 大学院・薬学系研究科, 教授 (40167987)
• Co-Investigator(Kenkyū-buntansha): INOUE Takao 東京大学, 大学院・薬学系研究科, 助教 (50361605)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥20,410,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥4,710,000); Fiscal Year 2010: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2009: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000); Fiscal Year 2008: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
• Keywords: 細胞情報伝達機構 / ホスファチジルイノシトール / アラキドン酸 / 脂肪酸転移酵素 / ボスファチジルイノシトール

Research Abstract

The fatty acid composition of phosphatidylinositol (PI) is unique in that most of PI fraction in mammalian tissues and cells constitutes the 1-stearoyl-2-arachidonoyl species. In this study, we identified acyltransferases, named LYCAT/ACL-10 and LPIAT1/MBOA-7,that incorporate stearic acid and arachidonic acid into lysoPI, respectively. Furthermore, we revealed the physiological significance of unique molecular species in PI by generating knockout worms and mice of these enzymes.

Research Products

• [Journal Article] Intracellular PLA1 and Acyltransferase, Which Are Involved in Caenorhabditis elegans Stem Cell Divisions, Determine the sn-1 fatty acyl Chain of Phosphatidylinositol (2010)
  • Author(s): Imae R., Inoue T., Kimura M., Kanamori T., H.Tomioka N., Kage-Nakadai E., Mitani S., Arai H.
  • Journal Title: Mol.Biol.Cell 21 Pages: 3114-3124
• [Journal Article] Decrease in membrane phospholipid unsaturation induces unfolded protein response (2010)
  • Author(s): Ariyama H., Kono N., Matsuda S., Inoue T., Arai H.
  • Journal Title: J.Biol.Chem. 221 Pages: 87-95
• [Journal Article] Intracellular PLA, and acyltransferase, which are involved in Celegans stem cell divisions, determine the sn-1 fatty acyl chain of phosphatidylinositol (2010)
  • Author(s): Imae R.
  • Journal Title: Mol.Biol.Cell Volume: 21 Pages: 3114-3124
  • Peer Reviewed
• [Journal Article] Multivesicular body formation requires OSBP-related proteins and cholesterol (2010)
  • Author(s): Kobuna H.
  • Journal Title: PLoS Genetics Volume: 6
  • 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
  • Journal Title: PLoS ONE 5
  • Peer Reviewed
• [Journal Article] Functional analysis of GS28, an intra-Golgi SNARE, in C.elegans (2009)
  • Author(s): Maekawa M.
  • Journal Title: Genes Cells 14 Pages: 1003-1013
  • Peer Reviewed
• [Journal Article] Nematode Homologue of PQBP1, a Mental Retardation Causative Gene, Is Involved in Lipid Metabolism (2009)
  • Author(s): Takahashi K
  • Journal Title: PloS One 4
  • Peer Reviewed
• [Journal Article] C.elegans mboa-7, a member of the MBOAT family, is required for selective incorporation of polyunsaturated fatty acids into phosphatidylinositol. (2008)
  • Author(s): Lee H.C., Inoue T., Imae R., Kono N., Shirae S., Matsuda S., Gengyo-Ando K., Mitani S., Arai H.
  • Journal Title: Mol.Biol.Cell 19 Pages: 1174-1184
• [Journal Article] β-Catenin asymmetry is regulated by PLA1 and retrograde traffic in C.elegans stem cell divisions. (2008)
  • Author(s): Kanamori T., Inoue T., Sakamoto T., Gengyo-Ando K., Tsujimoto M., Mitani S., Sawa H., Aoki J., Arai H.
  • Journal Title: EMBO J. 27 Pages: 1647-1657
• [Journal Article] A member of the membrane-bound O-acyltransferase (MBOAT) family encodes a lysophospholipid acyltransferase with broad substrate specificity. (2008)
  • Author(s): Matsuda S., Inoue T., Lee H.C., Kono N., Tanaka F., Gengyo-Ando K., Mitani S., Arai H.
  • Journal Title: Genes to Cells 13 Pages: 879-888
• [Journal Article] Caenorhabditis elegans mboa-7, a Member of the MBOAT Family, Is Required for Selective Incorporation of Polyunsaturated Fatty. Acids into Phosphatidylinositol (2008)
  • Author(s): Lee HC
  • Journal Title: Mol Biol Cell 19 Pages: 1174-1184
  • Peer Reviewed
• [Journal Article] Protection against oxidative stress-induced hepatic injury by intracellular type II platelet-activating factor acetylhydrolase by metabolism of oxidized phospholipids in vivo. (2008)
  • Author(s): Kono N
  • Journal Title: Journal of Biological Chemistry 283 Pages: 1628-1636
  • Peer Reviewed
• [Journal Article] β-catenin asymmetry is regulated by PLA(1) and retrograde traffic in C. elegans stem cell divisions (2008)
  • Author(s): Kanamori T
  • Journal Title: EMBO Journal 27 Pages: 1647-1657
  • Peer Reviewed
• [Journal Article] Member of the membrane-bound O-acyltransfe rase (MBOAT) family encodes a lysophospholipid acyltransferase with broad substrate specificity (2008)
  • Author(s): Matsuda S
  • Journal Title: Genes to Cells 13 Pages: 879-888
  • Peer Reviewed
• [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: 2010-12-09
• [Presentation] Functions of PUFA-containing phospholipids in C.elegans (2010)
  • Author(s): 松田真治
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] 線虫C.elegansを用いた生体膜脂質の機能解析 (2010)
  • Author(s): 井上貴雄
  • Organizer: 第32回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 富山
  • Year and Date: 2010-11-30
• [Presentation] Intracellular PLAl and acyltransferase, which are involved in C.elegans stem cell divisions, determine the sn-1 fatty acyl chain of phosphatidylinositol (2010)
  • Author(s): Rieko Imae
  • Organizer: 4th East Asia C.elegans Meeting
  • Place of Presentation: 東京
  • Year and Date: 2010-07-13
• [Presentation] Genetic analysis of phospholipid acyltransferases using C.elegans as a model organism (2010)
  • Author(s): Hiroyuki Arai
  • Organizer: FASEB SUMMER RESERCH CONFERENCES
  • Place of Presentation: Colorado, USA
  • Year and Date: 2010-06-27
• [Presentation] 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): Takao Inoue
  • Organizer: FASEB SUMMER RESERCH CONFERENCES
  • Place of Presentation: Colorado, USA
  • Year and Date: 2010-06-27
• [Presentation] Identification of acyltransferases responsible for PUFA incorporation into membrane phospholipids (2010)
  • Author(s): Hyeon-Cheol
  • Organizer: FASEB SUMMER RESERCH CONFERENCES
  • Place of Presentation: Colorado, USA
  • Year and Date: 2010-06-27
• [Presentation] 線虫C.elegansを用いた脂肪酸リモデリング酵素の包括的解析 (2010)
  • Author(s): 井上貴雄
  • Organizer: 第52回日本脂質生化学会
  • Place of Presentation: 群馬
  • Year and Date: 2010-06-14
• [Presentation] C.elegans as a model for studying the biological functions of polyunsaturated fatty acyl chain in membrane phospholipids (2010)
  • Author(s): 松田真治
  • Organizer: Keystone Symposia Conference
  • Place of Presentation: 京都
  • Year and Date: 2010-06-08
• [Presentation] Identification of enzymes which determine the fatty acid composition of phosphatidylinositol (2010)
  • Author(s): Inoue T., Arai H.
  • Organizer: BMB2010
  • Place of Presentation: Hyogo
• [Presentation] Functional analysis of membrane lipids using C.elegans (2010)
  • Author(s): Inoue T., Arai H.
  • Organizer: The 32th symposium on the Drugs-Membranes Interaction
  • Place of Presentation: Toyama
• [Presentation] Genetic analysis of phospholipid acyltransferases using C.elegans as a model organism (2010)
  • Author(s): 新井洋由
  • Organizer: FASEB Summer Research Conference Phospholipid Metabolism : Disease, Signal Transduction, and Membrane Dynamics
  • Place of Presentation: Colorado
• [Presentation] Comprehensive analysis of enzymes involved in phospholipid fatty acid remodeling (2010)
  • Author(s): Inoue T., Arai H.
  • Organizer: The 52th Japanese Conference on the Biochemistry of Lipids
  • Place of Presentation: Gunma
• [Presentation] LysoPI特異的脂肪酸転移酵素LPIATの哺乳類における機能解析 (2009)
  • Author(s): 中崎康子
  • Organizer: ファーマ・バイオフォーラム2009
  • Place of Presentation: 名古屋
  • Year and Date: 2009-11-15
• [Presentation] Identification of acyltransferases responsible for arachidonic acidincorporation into membrane phosholipids (2009)
  • Author(s): Hiroyuki Arai
  • Organizer: International Conference Bioactive Lipids in Cancer
  • Place of Presentation: Cancun Mexico
  • Year and Date: 2009-10-27
• [Presentation] リソホスファチシルイノシトール特異的脂肪酸転移酵素:mboa-7/LPIATの機能解析 (2009)
  • Author(s): 李賢哲
  • Organizer: 日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-21
• [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: 日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-21
• [Presentation] 生体膜リン脂質における高度不飽和脂肪酸鎖の機能 (2009)
  • Author(s): 新井洋由
  • Organizer: 日本脂質栄養学会
  • Place of Presentation: 東京
  • Year and Date: 2009-09-05
• [Presentation] 生体膜リン脂質多様性の構築機構 (2009)
  • Author(s): 新井洋由
  • Organizer: 第50回新潟生化学懇話会
  • Place of Presentation: 新潟市
  • Year and Date: 2009-06-27
• [Presentation] 生体膜リン脂質多様性の構築機構 (2009)
  • Author(s): 新井洋由
  • Organizer: 新潟生化学懇話会
  • Place of Presentation: 新潟
  • Year and Date: 2009-06-27
• [Presentation] C.elegans as a model studying the biological functions of PUFA in membrane phospholipids (2009)
  • Author(s): Takao Inoue
  • Organizer: PLM2009
  • Place of Presentation: 東京
  • Year and Date: 2009-05-26
• [Presentation] mboa-7/LPIAT is required for selective incorporation of polyunsaturated fatty acids into phosphatidylinositol (2009)
  • Author(s): Yasuko Nakasaki
  • Organizer: PLM2009
  • Place of Presentation: 東京
  • Year and Date: 2009-05-26
• [Presentation] Identification of acyltransferases responsible for arachidonic acid incorporation into membrane phospholipids (2009)
  • Author(s): Arai H., Inoue T.
  • Organizer: 11th International Conference Bioactive Lipids in Cancer, Inflammation and Related Diseases
  • Place of Presentation: Cancun Mexico
• [Presentation] Comprehensive analysis of phospholipid acyltransferases (2009)
  • Author(s): Inoue T., Arai H.
  • Organizer: The 82th Annual Meeting of the Japanese Biochemical Society
  • Place of Presentation: Hyogo
• [Presentation] C. elegans: a model for functional and molecular analysis of polyunsaturated fatty acid (2008)
  • Author(s): Takao Inoue
  • Organizer: BMB2008
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] Identification of lysophsphatidylinositol acyltransferase as a determinant of phosphatidylinositol molecular species (2008)
  • Author(s): Hiroyuki Arai
  • Organizer: 文部科学省ナショナルバイオリソースプロジェクト線虫・シンポジウム -Nematode: An ideal Model Organism for Functional Genomics-
  • Place of Presentation: 東京
  • Year and Date: 2008-11-05
• [Presentation] ホスファチジルイノシトール分子種形成の分子機構とその生物的意義 (2008)
  • Author(s): 新井洋由
  • Organizer: 第4回メタボロームシンポジウム
  • Place of Presentation: 鶴岡
  • Year and Date: 2008-10-31
• [Presentation] Functional and molecular analysis of polyunsaturated fatty acids using C.elegans (2008)
  • Author(s): Inoue T., Arai H.
  • Organizer: フォーラム2008:衛生薬学・環境トキシコロジー
  • Place of Presentation: 熊本
  • Year and Date: 2008-10-17
• [Presentation] Functional and molecular analysis of polyunsaturated fatty acids using C. elegans (2008)
  • Author(s): Takao Inoue
  • Organizer: フォーラム2008:衛生薬学・環境トキシコロジー
  • Place of Presentation: 熊本
  • Year and Date: 2008-10-17
• [Presentation] Identification of lysoPI acyltransferase as a determinant of phosphatidylinositol molecular species (2008)
  • Author(s): Arai H., Inoue T.
  • Organizer: FASEB SUMMER RESERCH CONFERENCES Phospholipid Metabolism : Disease Signal Transduction and Membrane Dynamics
  • Place of Presentation: New Haven,Connecticut
  • Year and Date: 2008-07-23
• [Presentation] Identification of lysophsphatidylinositol acyltransferase as a determinant of phosphatidylinositol molecular species (2008)
  • Author(s): Hiroyuki Arai
  • Organizer: FASEB SUMMER RESERCH CONFERENCES Phospholipid Metabolism: Disease Signal Transduction and Membrane Dynamics
  • Place of Presentation: New Haven, Connecticut
  • Year and Date: 2008-07-23
• [Presentation] C. elegans as a model for studying the biological functions of polyunsaturated fatty acyl chain in membrane phospholipids (2008)
  • Author(s): Hiroyuki Arai
  • Organizer: FASEB SUMMER RESERCH CONFERENCES Phospholipid Metabolism: Disease Signal Transduction and Membrane Dynamics
  • Place of Presentation: New Haven, Connecticut
  • Year and Date: 2008-07-23
• [Presentation] LysoPI特異的アシルトランスフェラーゼ(LPIAT)の同定と性状解析 (2008)
  • Author(s): Takao Inoue
  • Organizer: 第50回日本脂質生化学会
  • Place of Presentation: 徳島
  • Year and Date: 2008-06-06
• [Presentation] C. elegans mboa-7, a Member of the MBOAT family, is Required for Selective Incorporation of Polyunsaturated Fatty Acids into Phosphatidylinositol (2008)
  • Author(s): Takao Inoue
  • Organizer: East Asia Worm Meeting
  • Place of Presentation: Shanghai
  • Year and Date: 2008-04-19
• [Book] 実験医学(「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」)Vol.28, No.20 (2010)
  • Author(s): 井上貴雄, 新井洋由
• [Remarks] ホームページ等
  • URL: http://www.f.u-tokyo.ac.jp/~eisei/jp/Members.html