Determination of phosphorylation sites of the ceramide transport protein CERT, and a role of the phosphorylation

• Project/Area Number: 18370049
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: HANADA Kentaro National Institute of Infectious Diseases, 細胞化学部, 部長 (30192701)
• Co-Investigator(Renkei-kenkyūsha): KUMAGAI Keigo , 感染研・細胞化学部, 研究員 (40443105) ; TOMISHIGE Nario , 感染研・細胞化学部, 協力研究員 (10435711) ; KAWANO Miyuki , 感染研・細胞化学部, 協力研究員 (10454498)
• Project Period (FY): 2006 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥18,430,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥3,330,000); Fiscal Year 2009: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2008: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2007: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2006: ¥4,000,000 (Direct Cost: ¥4,000,000)
• Keywords: セラミド / スフィンゴミエリン / 脂質輸送 / 小胞体 / ゴルジ体 / スフィンゴ脂質 / 生体膜 / 阻害剤 / キナーゼ / リン酸化 / 多重リン酸化 / FFATモチーフ

Research Abstract

The ceramide transport protein CERT has a PH domain recognizing phosphatidylinositol 4-monophosphate and a START domain catalyzing intermembrane transfer of ceramide. We showed that multiple phosphorylations of CERT induce an auto-inhibitory interaction between the PH and START domains, thereby down-regulating the function of CERT, and that casein kinase Iγ2 is relevant to the phosphorylation.

Research Products

• [Journal Article] Crystal structures of the CERT START domain with inhibitors provide insights into the mechanism of ceramide transfer (2010)
  • Author(s): Norio Kudo
  • Journal Title: Journal of Molecular Biology 396 Pages: 245-251
  • Peer Reviewed
• [Journal Article] Casein kinase Iγ2 down-regulates trafficking of ceramide in the synthesis of sphingomyelin. (2009)
  • Author(s): Nario Tomishige, Keigo Kumagai, Jun Kusuda, Masahiro Nishijima, Kentaro Hanada
  • Journal Title: Mol. Biol. Cell 20 Pages: 348-357
• [Journal Article] CERT-mediated trafficking of ceramide. (2009)
  • Author(s): Kentaro Hanada, Keigo Kumagai, Nario Tomishige, Toshiyuki Yamaji
  • Journal Title: Biochim. Biophys. Acta 1791 Pages: 684-691
• [Journal Article] CERT-mediated trafficking of ceramide (2009)
  • Author(s): Kentaro Hanada
  • Journal Title: Biochimica et Biophysica Acta 1791 Pages: 684-691
  • Peer Reviewed
• [Journal Article] Characterization of mutant serine palmitoyltransferase 1 in LY-B cells (2009)
  • Author(s): Amin A.Momin
  • Journal Title: Lipids 44 Pages: 725-732
  • Peer Reviewed
• [Journal Article] Casein kinase Iγ2 down-regulates trafficking of ceramide in the synthesis of sphingomyelin (2009)
  • Author(s): N. Tomishige, K. Kumagai, J. Kusuda, M. Nishijima and K. Hanada
  • Journal Title: Mol. Biol. Cell 20 Pages: 348-357
• [Journal Article] Casein kinase Igamma2 down-regulates trafficking of ceramide in the synthesis of sphingomyelin (2009)
  • Author(s): Tomishige, N.
  • Journal Title: Molecular Biology of the Cell 20 Pages: 348-357
  • Peer Reviewed
• [Journal Article] Structural basis for specific lipid recognition by CERT responsible for nonvesicular trafficking of ceramide. (2008)
  • Author(s): Norio Kudo, Keigo Kumagai, Nario Tomishige, Toshiyuki Yamaji, Soichi Wakatsuki, Masahiro Nishijima, Kentaro Hanada, Ryuichi Kato
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 488-493
• [Journal Article] Protein phosphatase 2C is an endoplasmic reticulum integral membrane protein that dephosphorylates the ceramide transport protein CERT to enhance its association with organelle membranes (2008)
  • Author(s): S. Saito, H. Matsui, M. Kawano, K. Kumagai, N. Tomishige, K. Hanada, S. Echigo, S. Tamura and T. Kobayashi
  • Journal Title: J. Biol. Chem 283 Pages: 6584-6593
• [Journal Article] Structural basis for specific lipid recognition by CERT responsible for nonvesicular trafficking of ceramide (2008)
  • Author(s): N. Kudo, K. Kumagai, N. Tomishige, T. Yamaji, S. Wakatsuki, M. Nishijima, K. Hanada and R. Kato
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 488-493
• [Journal Article] Two sphingolipid transfer proteins, CERT and FAPP2 : Their roles in sphingolipid metabolism (2008)
  • Author(s): Yamaji, T.
  • Journal Title: IUBMB Life 60 Pages: 511-518
  • Peer Reviewed
• [Journal Article] Decreased ceramide transport protein (CERT) function alters sphingomyelin production following UVB irradiation (2008)
  • Author(s): Charruyer, A.
  • Journal Title: The Journal of Biological Chemistry 283 Pages: 16682-16692
  • Peer Reviewed
• [Journal Article] Structural basis for specific lipid recognition by CERT responsible for nonvesicular trafficking of ceramide (2008)
  • Author(s): Norio Kudo
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America 105 Pages: 488-493
  • Peer Reviewed
• [Journal Article] CERT and intracellular trafficking of ceramide. (2007)
  • Author(s): Kentaro Hanada, Keigo Kumagai, Nario Tomishige, Miyuki Kawano
  • Journal Title: Biochim. Biophys. Acta 1771 Pages: 644-653
• [Journal Article] Inter-organelle trafficking of ceramide is regulated by phosphorylation-dependent co-operativity between the PH and START domains of CERT. (2007)
  • Author(s): Keigo Kumagai, Miyuki Kawano, Fumiko Shinkai-Ouchi, Masahiro Nishijima, Kentaro Hanada
  • Journal Title: J. Biol. Chem. 282 Pages: 17758-17766
• [Journal Article] Inter-organelle trafficking of ceramide is regulated by phosphorylation-dependent co-operativity between the PH and START domains of CERT (2007)
  • Author(s): K. Kumagai, M. Kawano, F. Shinkai-Ouchi, M. Nishijima and K. Hanada
  • Journal Title: J. Biol. Chem 282 Pages: 17758-17766
• [Journal Article] CERT and intracellular trafficking of ceramide (2007)
  • Author(s): Kentaro Hanada
  • Journal Title: Biochimica et Biophysica Acta 1771 Pages: 644-653
  • Peer Reviewed
• [Journal Article] Interorganelle trafficking of ceramide is regulated by phosphorylation-dependent cooperativity between the PH and START domains of CERT (2007)
  • Author(s): Keigo Kumagai
  • Journal Title: The Journal of Biological Chemistry 282 Pages: 17758-17766
  • Peer Reviewed
• [Journal Article] Efficient trafficking of ceramide from the endoplasmic reticulum to the Golgi apparatus requires a VAMP-associated protein-interacting FFAT motif of CERT. (2006)
  • Author(s): Miyuki Kawano, Keigo Kumagai, Masahiro Nishijima, Kentaro Hanada
  • Journal Title: J. Biol. Chem. 281 Pages: 30279-30288
• [Journal Article] Efficient trafficking of ceramide from the endoplasmic reticulum to the Golgi apparatus requires a VAMP-associated protein-interacting FFAT motif of CERT (2006)
  • Author(s): M. Kawano, K. Kumagai, M. Nishijima and K. Hanada
  • Journal Title: J. Biol. Chem 281 Pages: 30279-30288
• [Journal Article] Discovery of the molecular machinery CERT for endoplasmic reticulum-to-Golgi trafficking of ceramide (2006)
  • Author(s): Kentaro Hanada
  • Journal Title: Molecular and Cellular Biochemistry 286 Pages: 23-31
• [Journal Article] Efficient trafficking of ceramide from the endoplasmic reticulum to the Golgi apparatus requires a VAMP-associated protein-interacting FFAT motif of CERT (2006)
  • Author(s): Miyuki Kawano
  • Journal Title: The Journal of Biological Chemistry 281 Pages: 30279-30288
• [Journal Article] 生命科学の中央舞台に歩み入る膜脂質ダイナミズム (2006)
  • Author(s): 花田賢太郎
  • Journal Title: 実験医学 24 Pages: 900-904
• [Journal Article] 脂質のオルガネラ間トラフィック (2006)
  • Author(s): 花田賢太郎
  • Journal Title: 実験医学 24 Pages: 912-917
• [Presentation] Regulation of CERT-mediated trafficking of ceramide (2009)
  • Author(s): K. Hanada
  • Organizer: 20th International Congress of Biochemistry and Molecular Biology
  • Place of Presentation: Kyoto, Japan.
  • Year and Date: 2009-06-22
• [Presentation] Regulation of CERT-mediated trafficking of ceramide (2009)
  • Author(s): K. Hanada
  • Organizer: 4th International Conference on Phospholipase A2 and Lipid Mediators (PLM2009)
  • Place of Presentation: Tokyo
• [Presentation] Regulation of CERT-mediated trafficking of ceramide (2009)
  • Author(s): Kentaro Hanada
  • Organizer: 4^<th> International Conference on Phospholipase A2 and Lipid Mediators(PLM2009)
  • Place of Presentation: Tokyo
• [Presentation] Regulation of CERT-mediated trafficking of ceramide (2009)
  • Author(s): K. Hanada
  • Organizer: 4^<th> International Conference on Phospholipase A2 and Lipid Mediators (PLM2009)
  • Place of Presentation: Tokyo
• [Presentation] Regulation of intracellular trafficking of ceramide by phosphorylayion of CERT (2009)
  • Author(s): K. Hanada
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会・合同大会
  • Place of Presentation: 横浜
• [Presentation] セラミドの細胞内選別輸送 (2008)
  • Author(s): 花田賢太郎
  • Organizer: 第19回フォーラム・イン・ドージン
  • Place of Presentation: 熊本
  • Year and Date: 2008-11-28
• [Presentation] Regulation of CERT-mediated trafficking of ceramide (2007)
  • Author(s): Kentaro Hanada
  • Organizer: 48^<th> International Conference on the Bioscience of Lipids
  • Place of Presentation: フィンランド
  • Year and Date: 2007-09-07
• [Presentation] CERT and ceramide trafficking (2007)
  • Author(s): K. Hanada
  • Organizer: Japan-Switzerland 2nd Joint Seminar on synthesis and trafficking of glycolipids and glycolipid anchored proteins
  • Place of Presentation: Tsukuba, Japan.
• [Presentation] Regulation of CERT-mediated trafficking of ceramide (2007)
  • Author(s): K. Hanada
  • Organizer: 48th International Conference on the Bioscience of Lipids
  • Place of Presentation: Turku, Finland.
• [Presentation] Regulation of CERT-mediated trafficking of ceramide (2007)
  • Author(s): K. Hanada
  • Organizer: 48^<th> International Conference on the Bioscience of Lipids
  • Place of Presentation: Turku, Finland
• [Presentation] Regulation of CERT-mediated trafficking of ceramide (2006)
  • Author(s): K. Hanada
  • Organizer: 20^<th> International Congress of Biochemistry and Molecular Biology
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2006-06-22
• [Presentation] Regulation of intracellular trafficking of ceramide (2006)
  • Author(s): K. Hanada
  • Organizer: FEBS special meeting, New concepts in lipidology: from lipidomics to disease
  • Place of Presentation: Noordwijkerhout, The Netherlands.
• [Presentation] Regulation of intracellular trafficking of ceramide, FEBS special meeting (2006)
  • Author(s): K. Hanada
  • Organizer: New concepts in lipidology : from lipidomics to disease
  • Place of Presentation: Noordwijkerhout, The Netherlands