A genetic biochemical search and analysis for factors involved in glycosphingolipid metabolism and traffic

• Project/Area Number: 20770114
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: YAMAJI Toshiyuki National Institute of Infectious Diseases, 細胞化学部, 主任研究官 (50332309)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: スフィンゴ糖脂質 / 志賀毒素 / 糖転移酵素 / トランスゴルジネットワーク / 糖鎖 / 脂質 / 細菌毒素 / 代謝 / スクリーニング

Research Abstract

We performed genetic biochemical screenings with shiga toxin to look for new factors that affect glycosphingolipid (GSL) metabolism and its intracellular traffic. As a molecule to reduce Gb3, the shiga toxin receptor, we isolated the COOH-terminus region of GRINA, a member of TMBIM family, which was named GRINA-C. Overexpression of GRINA-C and FAIM2, another TMBIM family member, affected the amount of Gb3 synthase and its intracellular localization, suggesting a new type of regulation of glycosyltransferases in GSL metabolism.

Research Products

• [Journal Article] Transmembrane BAX inhibitor motif containing (TMBIM) family proteins perturb a trans-Golgi network enzyme, Gb3 synthase, and reduce Gb3 biosynthesis. (2010)
  • Author(s): Yamaji, T., Nishikawa, K., Hanada, K.
  • Journal Title: J.Biol.Chem. 285 Pages: 35505-35518
  • Peer Reviewed
• [Journal Article] Siglec-7 mediates non-apoptotic cell death independently of its immunoreceptor tyrosine-based inhibitory motifs in monocytic cell line U937. (2010)
  • Author(s): Mitsuki, M., Nara, K., Yamaji, T., Enomoto A., Kanno, M., Yamaguchi, Y., Yamada, A., Waguri, S., Hashimoto, Y. (equal contribution)
  • Journal Title: Glycobiology 20 Pages: 395-402
  • Peer Reviewed
• [Journal Article] Transmembrane BAX inhibitor motif containing (TMBIM) family proteins perturbs a trans-Golgi network enzyme, Gb3 synthase, and reduces Gb3 biosynthesis (2010)
  • Author(s): Yamaji, T., Nishikawa, K., Hanada, K.
  • Journal Title: Journal of Biological Chemistry Volume: 285 Pages: 35505-35518
  • Peer Reviewed
• [Journal Article] Siglec-7 mediates nonapoptotic cell death independently of its immunoreceptor tyrosine-based inhibitory motifs in monocytic cell line U937 (2010)
  • Author(s): Mitsuki, M., Nara, K., Yamaji, T., Enomoto, A., Kanno, M., Yamaguchi, Y., Yamada, A., Waguri, S., Hashimoto, Y.
  • Journal Title: Glycobiology 20(3) Pages: 395-402
  • Peer Reviewed
• [Journal Article] CERT-mediated trafficking of ceramide. (2009)
  • Author(s): Hanada, K., Kumagai, K., Tomishige, N., Yamaji, T.
  • Journal Title: Biochim. Biophys.A cta 1791 Pages: 684-691
  • Peer Reviewed
• [Journal Article] CERT-mediated trafficking of ceramide (2009)
  • Author(s): Hanada, K., Kumagai, K., Tomishige, N., Yamaji, T.
  • Journal Title: Biochim Biophys Acta. 1791(7) Pages: 684-691
  • Peer Reviewed
• [Journal Article] CERT-mediated trafficking of ceramide (2009)
  • Author(s): Hanada, K., Kumagai, K., Tomishige, N., and Yamaji, T.
  • Journal Title: Biochim Biophys Acta. (印刷中)
  • Peer Reviewed
• [Journal Article] Two sphingolipid transfer proteins, CERT and FAPP2 : Their roles in sphingolipid metabolism. (2008)
  • Author(s): Yamaji, T., Kumagai, K., Tomishige, N., Hanada, K.
  • Journal Title: IUBMB Life 60 Pages: 511-518
  • Peer Reviewed
• [Journal Article] Two sphingolipid transfer proteins, CERT and FAPP2 : Their roles in sphingolimd metabolism (2008)
  • Author(s): Yamaji, T., Kumagai, K., Tomishige, N., and Hanada, K.
  • Journal Title: IUBMB Life. 60(8) Pages: 511-518
  • Peer Reviewed
• [Presentation] 糖鎖受容体Siglec-7を解する細胞死の分子機構の解明 (2010)
  • Author(s): 奈良清光、三ツ木元章、榎本綾子、菅野真由美、山口芳樹、二川了次、城谷圭朗、山地俊之、山田茜、和栗聡
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] 糖鎖受容体Siglec-7を解する細胞死の分子機構の解明 (2010)
  • Author(s): 奈良清光、三ツ木元章、榎本綾子、菅野真由美、山口芳樹、二川了次、城谷圭朗、山地俊之、山田茜、和栗聡
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • Year and Date: 2010-12-10
• [Presentation] Globotriaosylceramide (Gb3) is reduced by the expression of hydrophobic polypeptides including TMBIM family : Isolation of Shiga toxin-resistant genes (2010)
  • Author(s): Yamaji, T., Nishikawa, K., Hanada, K.
  • Organizer: The 28^<th> Naito Conference on Glycan Expression and Regulation[I]
  • Place of Presentation: 湘南
  • Year and Date: 2010-07-29
• [Presentation] Globotriaosylceramide (Gb3) is reduced by the expression of hydrophobic polypeptides including TMBIM family : Isolation of Shiga toxin-resistant genes (2010)
  • Author(s): Yamaji, T., Nishikawa, K., Hanada, K.
  • Organizer: The 28^<th> Naito Conference on Glycan Expression and Regulation [I]
  • Place of Presentation: 湘南国際村センター(神奈川県)
  • Year and Date: 2010-07-29
• [Presentation] Globotriaosylceramide (Gb3) is reduced by the expression of hydrophobic polypeptides including TMBIM family : Isolation of Shiga toxin-resistant genes (2010)
  • Author(s): Yamaji, T., Nishikawa, K., Hanada, K.
  • Organizer: The 27^<th> Naito Conference on Membrane Dynamics and Lipid Biology [I]
  • Place of Presentation: 札幌
  • Year and Date: 2010-07-01
• [Presentation] Globotriaosylceramide (Gb3) is reduced by the expression of hydrophobic polypeptides including TMBIM family : Isolation of Shiga toxin-resistant genes (2010)
  • Author(s): Yamaji, T., Nishikawa, K., Hanada, K.
  • Organizer: The 27^<th> Naito Conference on Membrane Dynamics and Lipid Biology [I]
  • Place of Presentation: シャトレーゼガトーキンクダムサッポロ(北海道)
  • Year and Date: 2010-07-01
• [Presentation] Siglec-7を介したU937細胞の細胞死に必要な細胞外領域の同定" 日本生化学会東北支部 (2010)
  • Author(s): 奈良清光、菅野真由美、三ツ木元章、山地俊之、山口芳樹、和栗聡、橋本康弘
  • Organizer: 第76回例会・シンポジウム
  • Place of Presentation: 福島
  • Year and Date: 2010-05-08
• [Presentation] Siglec-7を介したU937細胞の細胞死に必要な細胞外領域の同定 (2010)
  • Author(s): 奈良清光、菅野真由美、三ツ木元章、山地俊之、山口芳樹、和栗聡、橋本康弘
  • Organizer: 日本生化学会東北支部 第76回例会・シンポジウム
  • Place of Presentation: コラッセ福島(福島県)
  • Year and Date: 2010-05-08
• [Presentation] Binding specificity of siglec-7 prepared from various animal cell lines (2009)
  • Author(s): Ito, S., Ito, N., Tsuchida, A., Tokuda, N., Yagi, H., Kato, K., Mitsuki, M., Yamaji, T., Hashimoto, Y., Crocker, P.R., Furukawa K.
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-12-10
• [Presentation] 志賀毒素耐性遺伝子の単離 (2009)
  • Author(s): 山地俊之、西川喜代孝、花田賢太郎
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-24
• [Presentation] 志賀毒素耐性遺伝子の単離 (2009)
  • Author(s): 山地俊之、西川喜代孝、花田賢太郎
  • Organizer: 第29回日本糖質学会年会
  • Place of Presentation: 高山
  • Year and Date: 2009-09-11
• [Presentation] Binding specificity of siglec-7 prepared from various animal cell lines (2008)
  • Author(s): Ito, S., Ito, N., Tsuchida, A., Tokuda, N., Yagi, H., Kato, K., Mitsuki, M., Yamaji, T., Hashimoto, Y., Crocker, P. R., and Furukawa K.
  • Organizer: 日本分子生物学会年会・日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10