Regulation of membrane trafficking and cell polarity by changes in phospholipid asymmetry

• Project/Area Number: 18370074
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cell biology
• Research Institution: Hokkaido University
• Principal Investigator: YANAKA Kazuma Hokkaido University, 遺伝子病制御研究所, 教授 (60188290)
• Co-Investigator(Kenkyū-buntansha): KAMADA Konomi 北海道大学, 遺伝子病制御研究所, 准教授 (80312354) ; YAMAMOTO Takaharu 北海道大学, 遺伝子病制御研究所, 助教 (80312346)
• Project Period (FY): 2006 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥18,280,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥3,780,000); Fiscal Year 2008: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000); Fiscal Year 2007: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000); Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
• Keywords: 細胞極性 / 細胞骨格 / 細胞膜 / 脂質の非対称性 / 細胞内小胞輸送 / 酵母 / リン脂質トランスロケース / タンパク質リン酸化酵素 / Cdc42 small GTPase / P-type ATPase / リン酸質トランスロケース

Research Abstract

細胞は、細胞膜をはじめ、様々な生体膜から成り立っており、脂質は生体膜の必須な構成要素である。膜脂質の分布や輸送の異常は種々の病態を引き起こすことが示唆されているが、その詳細には不明な点が多い。本研究では、生体膜の脂質二重層において脂質の非対称性を制御するリン脂質輸送体(フリッペース)の機能について解析を行い、脂質非対称性の変化が細胞の極性形成や輸送小胞の形成を制御していることを明らかにした。

Research Products

• [Journal Article] Protein kinases Fpk1p and Fpk2p are novel regulators of phospholipid asymmetry (2008)
  • Author(s): Nakano K, Yamamoto T, Kishimoto T, Noji T, Tanaka K.
  • Journal Title: Mol. Biol. Cell 19 Pages: 1783-1797
  • Peer Reviewed
• [Journal Article] Protein Kinases Fpk1p and Fpk2p are Novel Regulators of Phospholipid Asymmetry. (2008)
  • Author(s): Nakano K., et. al.
  • Journal Title: Mol Biol Cell. (In press)
  • Peer Reviewed
• [Journal Article] Transbilayer phospholipid flipping regulates Cdc42p signaling during polarized cell growth via Rga GTPase-activating proteins (2007)
  • Author(s): Saito K, Fujimura-Kamada K, Hanamatsu H, Kato U, Umeda M, Kozminski KG, Tanaka K.
  • Journal Title: Dev. Cell 13 Pages: 743-751
  • NAID: 120000949917
  • Peer Reviewed
• [Journal Article] Endocytic recycling in yeast is regulated by putative phospholipid translocases and the Ypt31p/32p-Rcy1p pathway (2007)
  • Author(s): Furuta N, Fujimura-Kamada K, Saito K, Yamamoto T, Tanaka K.
  • Journal Title: Mol. Biol. Cell 18 Pages: 295-312
  • NAID: 120000967896
  • Peer Reviewed
• [Journal Article] Transbilayer Phospholipid Flipping Regulates Cdc42p Signaling during Polarized Cell Growth via Rga GTPase-Activeting Proteins. (2007)
  • Author(s): Saito K., et. al.
  • Journal Title: Dev Cell. 13 Pages: 743-751
  • Peer Reviewed
• [Journal Article] Endocytic Recycling in Yeast Is Regulated by Putative Phospholipid Translocases and the Ypt31p/32p-Rcylp Pathway. (2007)
  • Author(s): Furuta.N., et al.
  • Journal Title: Molecular Biology of the Cell 18 Pages: 295-312
• [Journal Article] Identification of novel mutations in ACT1 and SLA2 that suppress the actin cable-overproducing phenotype caused by overexpression of a dominant active form of Bni1p in Saccharomyces cerevisiae (2006)
  • Author(s): Yoshiuchi S, Yamamoto T, Sakane H, Kadota J, Mochida J, Asaka M, Tanaka K.
  • Journal Title: Genetics 173 Pages: 527-539
  • Peer Reviewed
• [Journal Article] Mutational analysis of the Lem3p-Dnf1p putative phospholipid-translocating P-type ATPase reveals novel regulatory roles for Lem3p and a carboxyl-terminal region of Dnf1p independent of the phospholipid-translocating activity of Dnf1p in yeast (2006)
  • Author(s): Noji T, Yamamoto T, Saito K, Fujimura-Kamada K, Kondo S, Tanaka K.
  • Journal Title: Biochem. Biophys. Res. Commun. 344 Pages: 323-331
  • NAID: 120000955300
  • Peer Reviewed
• [Journal Article] The functional relationship between the Cdc50p-Drs2p putative aminophospholipid translocase and the Arf GAP Gcs1p in vesicle formation in the retrieval pathway from yeast early endosomes to the TGN (2006)
  • Author(s): Sakane H, Yamamoto T, Tanaka K.
  • Journal Title: Cell Struct. Funct. 31 Pages: 87-108
  • NAID: 130004137511
  • Peer Reviewed
• [Journal Article] The functional relationship between the Cdc50p-Drs2p putative aminophospholipid translocase and the Arf GAP Gcs1p in vesicle formation in the retrieval pathway from yeast early endosomes to the TGN. (2006)
  • Author(s): Sakane.H., at al
  • Journal Title: Cell Structure and Function 31 Pages: 87-108
• [Journal Article] Mutational analysis of the Lem3p-Dnf1p putative phospholipid-translocating P-type ATPase reveals novel regulatory roles for Lem3p and a carboxyl-terminal region of Dnf1p independent of the phospholipid-translocating activity of Dnf1p in yeast. (2006)
  • Author(s): Noji.T., et al.
  • Journal Title: Biochemical and Biophysical Research Communications 344 Pages: 323-331
• [Journal Article] Identification of novel mutations in ACT1 and SLA2 that suppress the actin cable-overproducing phenotype caused by overexpression of a dominant active form of Bnilp in Saccharomyces cerevisiae. (2006)
  • Author(s): Yoshiuche.S., et al.
  • Journal Title: Genetics 173 Pages: 527-539
• [Presentation] フリッペースが制御する膜脂質非対称性とその細胞機能 (2009)
  • Author(s): 田中一馬
  • Organizer: 第82回日本生化学会大会合同大会
  • Place of Presentation: 神戸ホートアイランド(神戸市)
  • Year and Date: 2009-10-24
• [Presentation] Cellular functions of phospholipid flippases (2009)
  • Author(s): 田中一馬
  • Organizer: The fourth iCeMS International Symposium
  • Place of Presentation: ホテルフジタ京都(京都市)
  • Year and Date: 2009-05-28
• [Presentation] 脂質の膜脂質二重層間輸送が制御する細胞機能 (2008)
  • Author(s): 田中一馬
  • Organizer: BMB2008
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-10
• [Presentation] Roles of flippases in the endocytic recycling pathway in yeast (2008)
  • Author(s): 田中一馬
  • Organizer: Flippases 2008
  • Place of Presentation: Centro Stefano Franscini, Monte Verita Ascona, Switzerland
  • Year and Date: 2008-11-06
• [Book] 酵母のすべて 系統、細胞から分子まで(8章8 出芽における細胞極性形成) (2007)
  • Author(s): 大隅良典
  • Publisher: シュプリンガー・ジャパン株式会社
• [Book] バイオとナノの融合I新生命科学の基礎(第15章 細胞の膜リン脂質非対称性の役割( (2007)
  • Author(s): 北海道大学COE研究成果編集委員会
  • Publisher: 北海道大学出版会
• [Book] 酵母のすべて 系統、細胞から分子まで 8章8 出芽における細胞極性形成 (2007)
  • Author(s): 大隅良典
  • Publisher: シュプリンガー・ジャパン株式会社
• [Book] バイオとナノの融合I新生命科学の基礎 第15章 細胞の膜リン脂質非対称性の役割 (2007)
  • Author(s): 北海道大学COE研究成果編集委員会
  • Publisher: 北海道大学出版会