HCV (HCV) HCV. DDX1 ATPase (BSE) 2 C. Huh7 GLP

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1 PS C (BSE) HS. 1. HCV 1 DDX1 (HCV) ATPase/RNA DDX1 HCV DDX1 HCV N DDX1 ATPase HCV GLP C C Huh7 1

2 [ ] [ ( ): ( )] PrP sc neuro 2a ScN2a 2. PrP sc PrP sc 100 Glial Fibrilary Acidic Protein (GFAP) vacuolar ATPase A-subunit PrP sc CRMP-2 (Collapsin response mediator protein-2) PrP sc [ ] 24- U18666A PrP C PrP sc ED50 25nM ED50 1/20 1/40 U18666A ScN2a HMG-CoA mrna 24- PrP sc U18666A PrP sc U18666A BSE II (BSE) PrP BSE P9FD PrP sc BSE PrP BSE PrP BSE PrP BSE 1/1000 BSE ScN2a P9FD PrP sc P9FD PrP sc P9FD P9FD P9FD PrP sc 60 P9FD PrP sc 2

3 120 P9FD P9FD PrP sc [ ] 2. A Toll-like receptor PmrC A Toll-like receptor. 1. LPS LPS lipid A monophosphoryl lipid A PmrC A TLR4 A NF- B [ ] MPL LPS LPS Caspase-1 MPL Caspase-1 caspase-1 lipid A MPL caspase-1 caspase-11 lipid A MPL MPL TLR-4 MyD88/NF B LPS caspase-1 THP-1 MPL caspase-1 IL-1beta LPS TLR-4 MPL PS PSS PSS1 PSS2 PS CHO PS PS [ ] [ ] 2 SINV 3

4 PS SINV PS lacz SINV RNA CHO PS RNA SINV RNA PS PS RNA RNA PS CERT CERT CERT C5-DMB- 1:1 200 nm (LPS) CERT LPS [] RNA RNA PS [ ] CERT (1R,3R)-HPA12 CERT CHO -SM (1R,3R)-HPA12 CERT cdna 1-2. CERT (SM) SM CHO CERT CERT -SM (1R,3R)-HPA12 (1R,3R)-HPA12 CERT HPA12 (1R,3R)-HPA12 CERT [ ] CERT CERT (1) D-erythoro- (2) SM (3) [] CERT FFAT VAP FFAT CERT VAP CERT VAP CERT CERT FFAT CERT - FFAT FFAT CERT VAP - 4

5 [] CCKR CCKR CCK (PDT) PDT CCK CCKR [ ; Kaleeckal G. Harikumar, Vishwajeet Puri, Raman Deep Singh, Richard E. Pagano, and Laurence J. Miller ( )] PDT PDT [ ; Vladislav Dolgachev, M. Sharjeel Farooqui, Olga I. Kulaeva, Michael Tainsky, Biserka Nagy, Duska Separovic( )]] [; Bjørn Spilsberg, Kirsten Sandvig ( )] CB CHO CoA [; Arkaitz Carracedo, María Diez, Manuel Guzman, and Guillermo Velasco ( ) Math J.H. Geelen ( )] (CCK) CCKR G (IPC) IPC IPCS 5

6 IPCS [ 3 H]C2-96 TLC 96 GLUT1 T HTLV-1) GLUT1 [ ] Far Eastern Blotting MALDI-QIT-TOF-MS (matrix-assisted laser desorption/ ionization quadrupole ion trap IPCS (SMS) (SMS-1, SMS-2) (PC) SM IPCS IPCS/SMS SMS-1 SMS-2 C6-NBD- IPCS SMS IPCS [] time-of-flight mass spectrometry) MALDI-QIT-TOF-MS Far Eastern Blotting ( ) (TLC) PVDF MS TLC [ (. ) ] 10 GLUT) 12 GLUT1 GLUT3 GLUT1 F- GLUT1 MALDI-QIT-TOF-MS MALDI-QIT-TOF-MS DHBA 6

7 [ ] Golgi stack. Mol. Biol. Cell, 15, , ) M. Fukasawa, O. Varlamov, W. S. Eng, T. H. Sollner, and J. E. Rothman: Localization and activity of the SNARE Ykt6 determined by its regulatory domain and palmitoylation. Proc. Natl Acad Sci U S A, 101, , ) Y. Kondo, J. Hamada, C. Kobayashi, R. Nakamura, Y. Suzuki, R. Kimata, T. Nishimura, T. Kitagawa, N. Imura I ) V. Dolgachev, M. Sharjeel Farooqui, O. I. Kulaeva, M. Tainsky, B. Nagy, K. Hanada, and D. Separovic: De novo ceramide accumulation due to inhibition of its conversion to complex sphingolipids in apoptotic photosensitized cells. J. Biol. Chem., 279, , ) A. Carracedo, M.J.H. Geelen, M. Diez, K. Hanada, M. Guzmán, and G. Velasco: Ceramide sensitizes astrocytes to oxidative stress: protective role of cannabinoids. Biochem..J., 380, , ) Y. Tanaka, M. Takizawa, S. Igimi, and F. Amano: Enhanced release of prostaglandin D 2 during re-incubation of RAW macrophage-like cells after treatment of both lipopolysaccharide and non-steroidal anti-inflammatory drugs. Biol. Pharm. Bull., 27, , ) K. Kawasaki, R. K. Ernst, and S. I. Miller: 3-O-deacylation of lipid A by PagL, a PhoP/PhoQ-regulated deacylase of Salmonella typhimurium, modulates signaling through Toll-like receptor 4. J. Biol. Chem., 279, , ) K. Kawasaki, R. K. Ernst, and S. I. Miller: Deacylation and palmitoylation of lipid A by Salmonellae outer membrane enzymes modulate host signaling through Toll-like receptor 4. J. Endotoxin Res., 10, , ) A. Volchuk, M. Ravazzola, A. Perrelet, W. S. Eng, M. De Liberto, O. Varlamov, M. Fukasawa, T. Engel, T. H. Söllner, J. E. Rothman, and L. Orci: Countercurrent distribution of two distinct SNARE complexes mediating transport within the and S. Hara: Overexpression of hypoxia-inducible factor 1α in renal and bladder cancer cells increases tumorigenic potency, J. Urology, 173, , ) Y. Inoue, Y. Yamakawa, A. Sakudo, T. Kinumi, Y. Nakamura, Y. Matsumoto, K. Saeki, T. Kamiyama, T. Onodera, M. Nishijima: Infection route-independent accumulation of splenic abnormal prion protein. Jpn J Infect Dis., 58(2), 78-82, ) H. Furuoka, A. Yabuzoe, M. Horiuchi, Y. Tagawa, T. Yokoyama, Y. Yamakawa, M. Shinagawa and T. Sata: Effective antigen-retrieval for immunohistochemical detection of abnormal isoform of prion protein in animals. Acta NeuroPathol., 109, , K. G. Harikumar, V. Puri, R. D. Singh, K. Hanada, R. E. Pagano, and L. J. Miller: Differential effects of modification of membrane cholesterol and sphingolipids on the conformation, function, and trafficking of the G protein-coupled cholecystokinin receptor. J. Biol. Chem., 280, , ) K. Kumagai, S. Yasuda, K. Okemoto, M. Nishijima, S. Kobayashi, and K. Hanada: CERT mediates intermembrane transfer of various molecular species of ceramides. J. Biol. Chem., 280, , ) B. Spilsberg, K. Hanada, and K. Sandvig: Diphtheria toxin translocation across cellular membranes is regulated by sphingolipids. Biochem. Biophys. Res. Commun., 329, , ) H. Kishida, Y. Sakasegawa, K. Watanabe, Y. Yamakawa, M. Nishijima, Y. Kuroiwa, N. S. Hachiya, and K. Kaneko: Non-glycosylphosphatidylinositol(GPI)-anchored recombinant prion protein with dominant-negative mutation inhibits PrP sc replication in vitro. J. Protein Folding Disord, 11, 14-20,

8 17) T. Ohsawa, M. Nishijima, and O. Kuge: Functional analysis of Chinese hamster phosphatidylserine synthase 1 ( ),,, 28-34, 2004 through systematic alanine mutagenesis. Biochem. J., 381, , ) Q. Lao, O. Kuge, T. Fukamachi, T. Kakegawa, H. Saito, M. Nishijima, and H. Kobayashi: An IκB-β COOH Terminal Region Protein Is Essential for the Proliferation of CHO Cells Under Acidic Stress. J. Cell. Physiol., 203, , ) K. Kawasaki, R. K. Ernst, and S. I. Miller: Inhibition of Salmonella enterica serovar Typhimurium lipopolysaccharide deacylation by aminoarabinose membrane modification. J. Bacteriol., in press 20) K. Kawasaki, R. K. Ernst, and S. I. Miller: Purification and characterization of deacylated and/or palmitoylated lipid A species unique to Salmonella typhimurium. J. Endotoxin Res., in press 21) Q. Lao, T. Fukamachi, H. Saito, O. Kuge, M. Nishijima, II ) K. Hanada: Nonvesicular ER-to-Golgi trafficking of ceramide by CERT having a PI4P- recognising PH domain, The 3rd Japanese Biochemical society Biofrontier Symposium, New Aspect of Phospholipid Biology 2004, , Kamakura, Japan 02) K. Hanada: Molecular machinery for intracellular trafficking of ceramide, American Society for Biochemistry and Molecular Biology 2004 Annual Meeting, , Boston, USA 03) K. Hanada: Pickup and delivery of ceramide by CERT, Sapporo Sphingolipid Symposium, , Sapporo, Japan 04) K. Hanada: Molecular machinery for non-vesicular and H. Kobayashi: Requirement of an IκB-β COOH trafficking of ceramide in mammalian cells, Gordon Research terminal region protein for acidic-adaptation in CHO cells. J. Cell. Physiol., in press Conference on Glycolipid and Sphingolipid Biology, , Hyogo, Japan 05) K. Hanada: Discovery of the molecular machinery CERT 1) : : CERT,, 22, , ) : CERT,, 76, , ) :,, 40, , ) : ( ),,, , ), : BSE, 34(3), 44-46, ), : :,, 23, , ), : MD-2,, 7, , ) :, for ER-to-Golgi trafficking of ceramide, 5th International Conference on Lipid Binding Proteins, , Zao, Japan 06) K. Hanada: Molecular machinery for intracellular trafficking of ceramide, The 8th Membrane Forum, , Nagoya, Japan 07) K. Kawasaki, R. K. Ernst, and S. I. Miller: Lipid A deacylation by PagL: regulation of TLR4 signaling, 8th Biennial Conference of the International Endotoxin Society, , Kyoto Japan 08) K. Okemoto, K. Kawasaki, and M. Nishijima: Dephosphorylation of lipid A selectively reduces its activity to induce IL-1β production, 8th Biennial Conference of the International Endotoxin Society, , Kyoto, Japan 09) Y. Yamakawa, K. Hagiwara, K. Nohtomi, Y. Nakamura, Y. Higuchi, Y. Sato, T. Sata, and Expert Committee for BSE Diagnosis, Ministry of Health, Labour and Welfare of Japan: BSE inspection in Japan and finding of atypical PK-resistant prion protein (PrPRES) in an apparently healthy 23-month-old-holstein steer in Japan: First International 8

9 Conference of the European Network of Excellence NeuroPrion Prion , Paris 10) M. Fukasawa, S. Sato, Y. Yamakawa, T. Natsume, T. Suzuki, I. Shoji, H. Aizaki, T. Miyamura, and M. Nishijima: Proteomic profiling of lipid droplet proteins in HCV core-expressing hepatoma cell lines, 11th International Symposium on Hepatitis C Virus and Related Viruses, , Heidelberg, Germany 11) M. Shirakura, I. Shoji, T. Ichimura, R. Suzuki, T. Suzuki, Y. Sugiyama, T. Shimoji, K. Murakami, S. Sato, M. Fukasawa, Y. Yamakawa, M. Nishijima, and T. Miyamura: Proteomic analysis of Hepatitis C virus core-interacting proteins using a novel tandem affinity purification tag and mass spectrometry, 11th International Symposium on Hepatitis C virus and Related Viruses, , Heidelberg, Germany 09),, : CERT ),,,,,, : Neuroblastoma N2a cells stably expressing MHM2-tagged prion protein (PrP) for the analysis of the conformational conversion of PrP, 77, ), O. Varlamov, W. S. Eng, T. H. Sollner, J. E. Rothman: Localization and Activity of the SNARE Ykt6 Determined by its Regulatory Domain and Palmitoylation SNARE Ykt6 ), 77, ) : LPS 2. 01) : ) : ) : BSE,, , 04) : ) : : ) : :, 3 HTLV/ATL,,, ( ) 07),, :, 26, ( ) 08) : Molecular machinery for intracellular trafficking of the lipid ceramide , ) ),,,, : Mycoplasma penetrans,, ( ) 15) : C,, ),,,,,,,,, : C, 125, ),, :, 125, ) :, 125, ( ) 19),,, : 9

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