Screening and evaluation for molecules involved in cholestrerol transport

• Project/Area Number: 24790104
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Ishitsuka Reiko 国立研究開発法人理化学研究所, 小林脂質生物学研究室, 専任研究員 (60342747)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: コレステロール

Outline of Final Research Achievements

Cholesterol is a major component of lipids on plasma membranes and plays an important role on the formation of lipid rafts. The cholesterol content and distribution in cells is properly regulated. To examine know how intracellular cholesterol traffic and distribution are regulated, we screened chemical compounds involved in cholesterol traffic and distribution using a cholesterol-binding probe. We screened compounds that decrease the cholesterol probe-binding to the plasma membrane. We obtained compounds which inhibited cholesterol synthesis or cholesterol transport from the ER to the plasma membrane, or accumulated cholesterol in the late endosomes. We also got a compound which binds to liposomes and regulates the formation of the lipid domain.

Research Products

• [Journal Article] Detectors for evaluating the cellular landscape of sphingomyelin- and cholesterol-rich membrane domains (2016)
  • Author(s): Kishimoto T*, Ishitsuka R*, Kobayashia T. * equally contributed
  • Journal Title: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids Volume: in press Issue: 8 Pages: 812-829
  • DOI: 10.1016/j.bbalip.2016.03.013
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Evaluation of aegerolysins as novel tools to detect and visualize ceramide phosphoethanolamine, a major sphingolipid in invertebrates (2015)
  • Author(s): Bhat HB, Ishitsuka R, Inaba T, Murate M, Abe M, Makino A, Kohyama-Koganeya A, Nagao K, Kurahashi A, Kishimoto T, Tahara M, Yamano A, Nagamune K, Hirabayashi Y, Juni N, Umeda M, Fujimori F, Nishibori K, Yamaji-Hasegawa A, Greimel P, Kobayashi T.
  • Journal Title: FASEB J Volume: 29(9) Issue: 9 Pages: 3920-34
  • DOI: 10.1096/fj.15-272112
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Targeting cholesterol in a liquid-disordered environment by theonellamides modulates cell membrane order and cell shape. (2015)
  • Author(s): Arita Y, Nishimura S, Ishitsuka R, Kishimoto T, Ikenouchi J, Ishii K, Umeda M, Matsunaga S, Kobayashi T, Yoshida M
  • Journal Title: Chemistry and Biology Volume: 22 Issue: 5 Pages: 604-610
  • DOI: 10.1016/j.chembiol.2015.04.011
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of the transbilayer movement of diacylglycerol in the plasma membrane (2014)
  • Author(s): Ueda Y, Ishitsuka R, Hullin-Matsuda F, Kobayashi T.
  • Journal Title: Biochimie. Volume: 107 Pages: 45-50
  • Peer Reviewed / Open Access
• [Journal Article] Binding of a pleurotolysin ortholog from Pleurotus eryngii to sphingomyelin and cholesterol-rich membrane domains. (2013)
  • Author(s): Bhat H B, Kishimoto T, Abe M, Makino A, Inaba T, Murate M, Dohmae N, Kurahashi A, Nishibori K, Fujimori F, Greimel P, Ishitsuka R, Kobayashi T.
  • Journal Title: Journal of Lipid Research Volume: 54 Issue: 10 Pages: 2933-2943
  • DOI: 10.1194/jlr.d041731
  • Peer Reviewed
• [Presentation] 脂質ドメインと膜秩序を変化させる化合物のスクリーニングと解析 (2015)
  • Author(s): 石塚玲子、小林俊秀
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド・神戸市・兵庫県
  • Year and Date: 2015-12-01
• [Presentation] 細胞内コレステロール代謝や局在に関わる化合物のスクリーニング (2013)
  • Author(s): 石塚玲子、斎藤臣雄、長田裕之、岩下淑子、小林俊秀
  • Organizer: 第８６回日本生化学会大会
  • Place of Presentation: 横浜