Molecular Species of phosphoinositides and their functions

• Project/Area Number: 24390067
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Akita University
• Principal Investigator: SASAKI Junko 秋田大学, 医学(系)研究科(研究院), 准教授 (30333371)
• Co-Investigator(Renkei-kenkyūsha): NAKANISHI Hiroki 秋田大学, 大学生体情報研究センター, 助教 (10466740)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2014: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2013: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2012: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: 細胞内シグナル伝達 / イノシトールリン脂質

Outline of Final Research Achievements

We established the sensitive method for measuring phosphoinositides (PIs) by mass spectrometry, and found that various PIs molecular species were exist in cells. Through the analyses of the cells with overexpression or knockout of PIs metabolizing enzymes, it was suggested that each PIs species might have different cellular functions.

Research Products

• [Journal Article] INPP4B is a PtdIns(3,4,5)P3 phosphatase that can act as a tumor suppressor. (2015)
  • Author(s): Kofuji S, Kimura H, Nakanishi H, Nanjo H, Takasuga S, Liu H, Eguchi S, Nakamura R, Itoh R, Ueno N, Asanuma K, Huang M, Koizumi A, Habuchi T, Yamazaki M, Suzuki A, Sasaki J, Sasaki T.
  • Journal Title: Cancer Discovery Volume: in press
• [Journal Article] In vivo role of INPP4B in tumor and metastasis suppression through regulation of PI3K/AKT signaling at endosomes. (2015)
  • Author(s): Chew CL, Lunardi A, Gulluni F, Ruan DT, Chen M, Salmena L, Nishino M, Papa A, Ng C, Fung J, Clohessy JG, Sasaki J, Sasaki T, Bronson RT, Hirsch E, Pandolfi PP
  • Journal Title: Cancer Discovery Volume: in press
• [Journal Article] Loss of INPP4B causes a DNA repair defect through loss of BRCA1, ATM and ATR and can be targeted with PARP inhibitor treatment. Oncotarget. (2015)
  • Author(s): Ip LR, Poulogiannis G, Viciano FC, Sasaki J, Kofuji S, Spanswick VJ, Hochhauser D, Hartley JA, Sasaki T, Gewinner CA.
  • Journal Title: Oncotarget Volume: in press
• [Journal Article] Dachsous-Dependent Asymmetric Localization of Spiny-Legs Determines Planar Cell Polarity Orientation in Drosophila. (2014)
  • Author(s): Ayukawa T., Akiyama M., Mummery-Widmer JL., Stoeger T., Sasaki J., Knoblich JA., Senoo H., Sasaki T., Yamazaki M.
  • Journal Title: Cell Rep. Volume: 8 Issue: 2 Pages: 610-621
  • DOI: 10.1016/j.celrep.2014.06.009
  • Peer Reviewed / Open Access
• [Journal Article] Phosphatidic acid-preferring phospholipase A1 regulates mitochondrial dynamics. (2014)
  • Author(s): Baba T, Kashiwagi Y, Arimitsu N, Kogure T, Edo A, Maruyama T, Nakao K, Nakanishi H, Kinoshita M, Frohman MA, Yamamoto A, Tani K.
  • Journal Title: Journal of Biological Chemistry Volume: 289 Issue: 16 Pages: 11497-11511
  • DOI: 10.1074/jbc.m113.531921
  • Peer Reviewed / Open Access
• [Journal Article] Very-long-chain polyunsaturated fatty acids accumulate in phosphatidylcholine of fibroblasts from patients with Zellweger syndrome and acyl-CoA oxidase1 deficiency (2014)
  • Author(s): Yuichi Abe, Masanori Honsho, Hiroki Nakanishi, Ryo Taguchi, Yukio Fujiki
  • Journal Title: BBA - Molecular and Cell Biology of Lipids Volume: 1841 Issue: 4 Pages: 610-619
  • DOI: 10.1016/j.bbalip.2014.01.001
  • Peer Reviewed / Open Access
• [Journal Article] リピドミクスの分析技術と将来展望 (2014)
  • Author(s): 中西広樹
  • Journal Title: オレオサイエンス誌 Volume: 8 Pages: 321-327
  • NAID: 130005308258
• [Journal Article] A Ca2+-dependent signaling circuit regulates influenza A virus internalization and infection (2013)
  • Author(s): Fujioka Y, Tsuda M, Nanbo A, Hattori T, Sasaki J, Sasaki T, Miyazaki T, Ohba Y
  • Journal Title: Nature Co㎜unnications Volume: 4 Issue: 1 Pages: 2-763
  • DOI: 10.1038/ncomms3763
  • Peer Reviewed
• [Journal Article] Deletion of autophagy-related 5 (Atg5) and Pik3c3 genes in the lens causes cataract independent of programmed organelle degradation. (2013)
  • Author(s): 森下英晃、江口賢史、木村洋貴、佐々木純子、酒巻有里子、Robinson ML、佐々木雄彦、水島昇
  • Journal Title: J Biol Chem. Volume: 288 Issue: 16 Pages: 11436-47
  • DOI: 10.1074/jbc.m112.437103
  • Peer Reviewed
• [Journal Article] Lipidomic analysis of brain tissues and plasma in a mouse model expressing mutated human amyloid precursor protein/tau for Alzheimer's disease. (2013)
  • Author(s): Tajima Y, Ishikawa M, Maekawa K, Murayama M, Senoo Y, Nishimaki-Mogami T, Nakanishi H, Ikeda K, Arita M, Taguchi R, Okuno A, Mikawa R, Niida S, Takikawa O, Saito Y.
  • Journal Title: Lipids Health Dis Volume: 12 Issue: 1 Pages: 68-68
  • DOI: 10.1186/1476-511x-12-68
  • Peer Reviewed
• [Journal Article] Lymphoid tissue phospholipase A2 group IID resolves contact hypersensitivity by driving antiinflammatory lipid mediators. (2013)
  • Author(s): Miki Y, Yamamoto K, Taketomi Y, Sato H, Shimo K, Kobayashi T, Ishikawa Y, Ishii T, Nakanishi H, Ikeda K, Taguchi R, Kabashima K, Arita M, Arai H, Lambeau G, Bollinger JM, Hara S, Gelb MH, Murakami M.
  • Journal Title: J Exp Med. Volume: 210 Issue: 6 Pages: 1217-1234
  • DOI: 10.1084/jem.20121887
  • Peer Reviewed
• [Journal Article] Molecular species of phospholipids with very long chain fatty acids in skin fibroblasts of Zellweger syndrome. (2013)
  • Author(s): Hama K, Nagai T, Nishizawa C, Ikeda K, Morita M, Satoh N, Nakanishi H, Imanaka T, Shimozawa N, Taguchi R, Inoue K, Yokoyama K.
  • Journal Title: Lipids Volume: 48 Issue: 12 Pages: 1253-1267
  • DOI: 10.1007/s11745-013-3848-5
  • Peer Reviewed
• [Journal Article] Critical roles of type III phosphatidylinositol phosphate kinase in murine embryonic visceral endoderm and adult intestine (2012)
  • Author(s): Takasuga , Wada et al.
  • Journal Title: PNAS 110 Volume: 1726-1731 Issue: 5 Pages: 1726-31
  • DOI: 10.1073/pnas.1213212110
  • Peer Reviewed
• [Journal Article] LPIAT1 regulates arachidonic acid content in phosphatidylinositol and is required for cortical lamination in mice. (2012)
  • Author(s): Lee, HC et al.
  • Journal Title: Mol. Biol. Cell Volume: 23 Issue: 24 Pages: 4689-4700
  • DOI: 10.1091/mbc.e12-09-0673
  • Peer Reviewed
• [Journal Article] Construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception. (2012)
  • Author(s): Neely GG
  • Journal Title: PLoS Genet. Volume: 8 Issue: 12 Pages: e1003071-e1003071
  • DOI: 10.1371/journal.pgen.1003071
  • Peer Reviewed
• [Presentation] The class III PI3K and phosphatidylinositol 3-phosphate ensure structural and functional integrity of cardiomyocytes (2015)
  • Author(s): Hirotaka Kimura, Satoshi Eguchi, Junko Sasaki, Takehiko Sasaki
  • Organizer: the 120th Annual Meeting of The Japanese Association of Anatomists, the 92nd Annual Meeting of The Physiological Society of Japan
  • Place of Presentation: 兵庫
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] The novel mechanism of tumor suppression by INPP4B (2015)
  • Author(s): Junko Sasaki, Satoshi Kofuji, Takahiro Kimura, Shunsuke Takasuga, Hiroki Nakanishi, Takehiko Sasaki
  • Organizer: 2nd International Symposium on Protein Modifications in Pathogenic Dysregulation of Signaling
  • Place of Presentation: 東京
  • Year and Date: 2015-01-23 – 2015-01-24
• [Presentation] Macrophage activation by phosphoinositides. (2013)
  • Author(s): Junko Sasaki
  • Organizer: Frontiers in Immunology & Inflammation: From Molecules to Disease
  • Place of Presentation: 東京
  • Year and Date: 2013-02-12
• [Presentation] マクロファージの活性化と慢性炎症 (2012)
  • Author(s): 佐々木純子
  • Organizer: 千里ライフサイエンスセミナー
  • Place of Presentation: 大阪(招待講演)
  • Year and Date: 2012-07-27
• [Presentation] 質量分析法によるホスホイノシタイドの解析
  • Author(s): 佐々木 純子
  • Organizer: 「修飾シグナル病」第3回公開シンポジウム シグナル伝達解析技術と数理モデルの最先端
  • Place of Presentation: 東京
  • Invited
• [Presentation] イノシトールリン脂質によるマクロファージの活性化と寿命制御
  • Author(s): 佐々木純子、中西広樹、高須賀俊輔、佐々木雄彦
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 神奈川
  • Invited
• [Presentation] Dual specificity phosphatases acting on acidic phospholipids
  • Author(s): 佐々木 雄彦, 高須賀 俊輔, 佐々木 純子, 鈴木 聡
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 神奈川
• [Presentation] ホスファチジルグリセロールリン酸（PGP）ホスファターゼの生理機能
  • Author(s): 高須賀俊輔、浅沼研、木村洋貴、高須賀緑、中西広樹、佐々木純子、 山崎正和、妹尾春樹、佐々木雄彦
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 神奈川
• [Presentation] イノシトールリン脂質によるマクロファージの活性化
  • Author(s): 佐々木 純子
  • Organizer: 第1回Academy of Aging and Cardiovascular-Diabetes Research
  • Place of Presentation: 東京
  • Invited
• [Presentation] 酸化関連脂質代謝物の高感度分析法の開発と応用
  • Author(s): 中西広樹
  • Organizer: 第５５回日本脂質生化学会
  • Place of Presentation: 宮城
• [Book] 医学のあゆみ (2014)
  • Author(s): 佐々木雄彦、中西広樹
  • Publisher: 医歯薬出版株式会社
• [Book] 別冊BIO Clinica 骨髄―末梢血による炎症の制御と修飾 (2013)
  • Author(s): 佐々木純子、佐々木雄彦
  • Publisher: 北隆館
• [Book] 実験医学別冊 (2013)
  • Author(s): 中西広樹
  • Publisher: 羊土社
• [Book] 遺伝子医学MOOK (2013)
  • Author(s): 中西広樹
  • Publisher: 医療総合出版
• [Remarks]
  • URL: http://www.med.akita-u.ac.jp/~bisei/
• [Remarks] http://www.med.akita-u.ac.jp/~bisei/