The identification of intact PI3P phosphatase and physiological role

• Project/Area Number: 26440020
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Akita University
• Principal Investigator: EGUCHI SATOSHI 秋田大学, 医学(系)研究科(研究院), 助教 (70457117)
• Co-Investigator(Renkei-kenkyūsha): Sasaki Takehiko 秋田大学, 医学系研究科, 教授 (50333365) ; Horie Yasuo 秋田大学, 医学系研究科, 講師 (30282164)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: イノシトールリン脂質 / 脱リン酸化酵素 / ホスファターゼ / フォスファターゼ / リン脂質

Outline of Final Research Achievements

Phosphoinositide generated by various phosphoinositide kinase and phosphatase have different physiological functions. PI3P and PI(3,5)P2 is important for nutrient signaling and vesicular trafficking, however, its physiological function remains unclear. Therefore, I generated knockout mice of MTMRs which dephosphorylates PI3P and PI(3,5)P2 in vitro. Analysis of these knockout mice revealed that deficiency of MTMRs caused lung cancer and cardiac hypertrophy.

Research Products

• [Journal Article] PKN2 is essential for mouse embryonic development and proliferation of mouse fibroblasts. (2017)
  • Author(s): Danno S, Kubouchi K, Mehruba M, Abe M, Natsume R, Sakimura K, Eguchi S, Oka M, Hirashima M, Yasuda H, Mukai H.
  • Journal Title: Genes Cells. Volume: 22 Issue: 2 Pages: 220-236
  • DOI: 10.1111/gtc.12470
  • Peer Reviewed
• [Journal Article] Vps34 regulates myofibril proteostasis to prevent hypertrophic cardiomyopathy. (2017)
  • Author(s): Kimura H, Eguchi S, Sasaki J, Kuba K, Nakanishi H, Takasuga S, Yamazaki M, Goto A, Watanabe H, Itoh H, Imai Y, Suzuki A, Mizushima N, Sasaki T
  • Journal Title: JCI Insight Volume: 2 Issue: 1 Pages: 89462-89478
  • DOI: 10.1172/jci.insight.89462
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [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 Issue: 7 Pages: 730-9
  • DOI: 10.1158/2159-8290.cd-14-1329
  • Peer Reviewed / Open Access
• [Presentation] タンパク質リン酸化酵素PKN2はマウスの初期発生に必須である。 (2016)
  • Author(s): 團野紗莉、崎村健司、江口賢史、Mona Mehruba、窪内康二、向井秀幸
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] A method for studying quality of phosphoinositides (2016)
  • Author(s): Takehiko Sasaki, Hiroki Nakanishi, Satoshi Eguchi, Masaki Ishikawa, Akira Suzuki, Junko Sasaki
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] ホスホイノシタイドの新しい解析方法 (2015)
  • Author(s): 中西 広樹、江口 賢史、石川 将己、鈴木 聡、佐々木 純子、佐々木 雄彦
  • Organizer: 第３８回日本分子生物学会年会、第８８回日本生化学会合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-04
• [Presentation] 心肥大におけるホスホイノシタイド代謝酵素Vps34のタンパク質分解機構の役割 (2015)
  • Author(s): 木村 洋貴、江口 賢史、久場 敬司、今井 由美、高須賀 俊輔、伊藤 玲悦、中村 亮太郎、中西 広樹、石川 将己、佐々木 純子、山崎 正和、佐々木 雄彦
  • Organizer: 第３８回日本分子生物学会年会、第８８回日本生化学会合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-03
• [Presentation] T細胞におけるホスホイノシタイド代謝酵素PIK3C3の生理的役割 (2014)
  • Author(s): 江口賢史、木村洋貴、佐々木純子、佐々木雄彦
  • Organizer: 第８７回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-18
• [Patent(Industrial Property Rights)] ホスホイノシタイド分離測定法の開発 (2017)
  • Inventor(s): 中西広樹、 佐々木雄彦、江口賢史、佐々木純子、中西貴代
  • Industrial Property Rights Holder: 秋田大学、ALTe
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017-03-16
• [Patent(Industrial Property Rights)] 新規リン脂質およびその利用 (2016)
  • Inventor(s): 江口賢史、佐々木雄彦、中西広樹、石川将己、上野紀子、佐々木純子
  • Industrial Property Rights Holder: 秋田大学、ALTe
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-07-22