Intracellular trafficking in the liver

• Project/Area Number: 26461002
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Osaka University
• Principal Investigator: Ryotaro Sakamori 大阪大学, 医学系研究科, 助教 (10644685)
• Co-Investigator(Kenkyū-buntansha): 巽 智秀 大阪大学, 医学系研究科, 講師 (20397699)
• Research Collaborator: GAO Nan Rutgers University, Associate Professor
• 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: 細胞内輸送 / Rab11a / 国際情報交換 / アメリカ合衆国 / 細胞極性

Outline of Final Research Achievements

Rab11a, one of the small GTPases, is required for intracellular trafficking. We hypothesized that Rab11a involves in intracellular trafficking of lipid; absorption, metabolism and excretion. Hepatocyte specific Rab11a knockout mice were produced and survived as long as normal control mice. High fat diet was given for producing the NAFLD model mice for analysis of lipid metabolism in the liver. Results of increase of body weight and lipid accumulation in knockout mice were obtained. Hepatocyte Rab11a was related with intracellular lipid accumulation.

Research Products

• [Int'l Joint Research] Rutgers大学(米国)
• [Int'l Joint Research] Rutgers University(米国)
• [Journal Article] Rab8a vesicles regulate Wnt ligand delivery and Paneth cell maturation at the intestinal stem cell niche. (2015)
  • Author(s): Das S, Yu S, Sakamori R, Vedula P, Feng Q, Flores J, Hoffman A, Fu J, Stypulkowski E, Rodriguez A, Dobrowolski R, Harada A, Hsu W, Bonder EM, Verzi MP, Gao N
  • Journal Title: Development Volume: 142(12) Issue: 12 Pages: 2147-2162
  • DOI: 10.1242/dev.121046
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Plasmalemma Vesicle Associated Protein Truncation Causes Lethal Protein-Losing Enteropathy in Humans. (2015)
  • Author(s): Sakamori R, Zhang L, Gao N.
  • Journal Title: Cell Mol Gastroenterol Hepatol. Volume: 1(4) Pages: 348-349
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The Hepatitis B Virus Genotype Affects the Persistence of Viral Replication in Immunodeficient NOG Mice. (2015)
  • Author(s): Yokoyama Y, Miyagi T, Hikita H, Yoshioka T, Mukai K, Nawa T, Sakamori R, Ohkawa K, Hiramatsu N, Takahashi T, Suemizu H, Ryo A, Tatsumi T, Takehara T.
  • Journal Title: PLoS One. Volume: 10(12) Issue: 12 Pages: e0144775-e0144775
  • DOI: 10.1371/journal.pone.0144775
  • Peer Reviewed / Open Access
• [Journal Article] Emergence of hepatitis C virus NS5A L31V plus Y93H variant upon treatment failure of daclatasvir and asunaprevir is relatively resistant to ledipasvir and NS5B polymerase nucleotide inhibitor GS-558093 in human hepatocyte chimeric mice. (2015)
  • Author(s): Kai Y, Hikita H, Tatsumi T, Nakabori T, Saito Y, Morishita N, Tanaka S, Nawa T, Oze T, Sakamori R, Yakushijin T, Hiramatsu N, Suemizu H, Takehara T.
  • Journal Title: J Gastroenterol. Volume: 50(11) Issue: 11 Pages: 1145-1151
  • DOI: 10.1007/s00535-015-1108-6
  • Peer Reviewed
• [Journal Article] Invariant natural killer T cell deficiency leads to the development of spontaneous liver inflammation dependent on γδT cells in mice. (2015)
  • Author(s): Nishio K, Miyagi T, Tatsumi T, Mukai K, Yokoyama Y, Yoshioka T, Sakamori R, Hikita H, Kodama T, Shimizu S, Shigekawa M, Nawa T, Yoshihara H, Hiramatsu N, Yamanaka H, Seino K, Takehara T.
  • Journal Title: J Gastroenterol. Volume: 50(11) Issue: 11 Pages: 1124-1133
  • DOI: 10.1007/s00535-015-1060-5
  • Peer Reviewed
• [Journal Article] Activation of the Mitochondrial Apoptotic Pathway Produces Reactive Oxygen Species and Oxidative Damage in Hepatocytes That Contribute to Liver Tumorigenesis. (2015)
  • Author(s): Hikita H, Kodama T, Tanaka S, Saito Y, Nozaki Y, Nakabori T, Shimizu S, Hayashi Y, Li W, Shigekawa M, Sakamori R, Miyagi T, Hiramatsu N, Tatsumi T, Takehara T.
  • Journal Title: Cancer Prev Res (Phila). Volume: 8(8) Issue: 8 Pages: 693-701
  • DOI: 10.1158/1940-6207.capr-15-0022-t
  • Peer Reviewed
• [Journal Article] TLR Sorting by Rab11 Endosome in Enterocyte Maintains Intestinal Epithelial-Microbial Homeostasis (2014)
  • Author(s): Shiyan Yu, Yingchao Nie, Byron Knowles, Ryotaro Sakamori, Ewa Stypulkowski, Chirag Patel, Soumyashree Das, Veronique Douard, Ronaldo P. Ferraris, Edward M.Bonder, James R. Goldenring, Y. Tomy Ip, Nan Gao
  • Journal Title: The EMBO Journal Volume: 33(17) Issue: 17 Pages: 1882-1895
  • DOI: 10.15252/embj.201487888
  • Peer Reviewed / Open Access
• [Journal Article] Global Ablation of Mouse Rab11a Impairs Early Embryogenesis and Matrix Metalloproteinase Secretion. (2014)
  • Author(s): Shiyan Yu, Ghassan Yehia, Juanfei Wang, Ewa Stypulkowski, Ryotaro Sakamori, Ping Jiang, Edith B Hernandez-Enriquez, Tracy S. Tran, Edward M. Bonder, Wei Guo, Nan Gao
  • Journal Title: J Biol Chem. Volume: 289(46) Issue: 46 Pages: 32030-32043
  • DOI: 10.1074/jbc.m113.538223
  • Peer Reviewed / Open Access
• [Journal Article] CDC42 inhibition suppresses progression of incipient intestinal tumors. (2014)
  • Author(s): Ryotaro Sakamori, Shiyan Yu, Xiao Zhang, Andrew Hoffman, Jiaxin Sun, Soumyashree Das, Pavan Vedula, Guangxun Li, Jiang Fu, Francesca Walker, Chung S. Yang, Zheng Yi, Wei Hsu, Da-Hai Yu, Lanlan Shen, Alexis J. Rodriguez, Makoto M. Taketo, Edward M. Bonder, Michael P. Verzi, Nan Gao
  • Journal Title: Cancer Research Volume: 74(19) Issue: 19 Pages: 5480-5492
  • DOI: 10.1158/0008-5472.can-14-0267
  • Peer Reviewed / Open Access
• [Presentation] Cdc42は腸管における癌幹細胞のニッチ形成に関与する (2014)
  • Author(s): 阪森亮太郎、巽智秀、竹原徹郎
  • Organizer: 第56回日本消化器病学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2014-10-23
• [Presentation] Colorectal cancer cells exploit the pleiotropic functions of Cell Division Cycle 42 for immediate pro-survival niche construction. (2014)
  • Author(s): Ryotaro Sakamori, Shiyan Yu, Jiaxin Sun, Xiao Zhang, Nan Gao
  • Organizer: Digestive Disease Week 2014
  • Place of Presentation: アメリカ合衆国シカゴ
  • Year and Date: 2014-05-04