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List of the 100 Selected Papers

Biology

83	Kitamura, H. 1; Kamon, H. 2; Sawa, S. 1; Park. SJ. 1; Katunuma, N.; Ishihara, K. 1,2; Murakami, M. 1; Hirano, T. 1,2 1 (Graduate School of Medicine) *2 (Graduate School of Frontier Bioscience) IL-6-STAT3 Controls Intracellular MHC Class II Alphabeta Dimer Level Through Cathepsin S Activity in Dendritic Cells Immunity, 23, 491-502 (2005) IL-6-STAT3 signaling reduced MHCII-dimer levels in DCs. IL-6-STAT3 activation decreased cystatin-C, an endogenous inhibitor of cathepsins, and enhanced cathepsin activities. Cathepsin-S inhibitors blocked reduction of MHCII-dimer in IL-6-treated DCs. Overexpression of cystatin-C suppressed IL-6-STAT3-mediated increase of cathepsin-S activity and reduction of MHCII-dimer levels in DCs. Cathepsin-S overexpression decreased intracellular MHCII-dimer levels, LPS-mediated surface expression of MHCII and suppressed CD4(+) T cell activation. IL-6-gp130-STAT3 signaling in vivo also decreased cystatin-C expression and reduced MHCII-dimer level in DCs.

84	Kashiwagi, H. ; Shiraga, M.; Kato, H.; Kamae, T.; Yamamoto, N.; Tadokoro, S.; Kurata, Y.; Tomiyama, Y.; Kanakura, Y. (Graduate School of Medicine) Negative Regulation of Platelet Function by a Secreted Cell Repulsive Protein, Semaphorin 3A Blood, 106, 913-921 (2005) The conquest of diseases caused by arterial thrombus, such as myocardial or cerebral infarction, is one of main goals in modern medicine, and platelets play crucial roles in arterial thrombus formation. In this paper, we reported that semaphorin (Sema) 3A, which is known as an axon guidance protein, binds to platelets and inhibits platelet functions via impairment of agonist-induced Rac1-dependent actin rearrangement. Thus, Sema3A and modulation of Sema3A-dependent signaling may be a new target of anti-platelet therapy.

85	Tachibanaki, S. 1,2; Arinobu, D. 1; Shimauchi-Matsukawa, Y. 1; Tsushima, S. 2; Kawamura, S. 1,2 1 (Graduate School of Frontier Biosciences) *2 (Graduate School of Science) Highly Effective Phosphorylation by G protein-coupled Receptor Kinase 7 of Light-activated Visual Pigment in Cones Proceedings of the National Academy of Sciences of the United States of America, 102, 9329-9334 (2005) Our visual system consists of two components, rods and cones. Cones mediate daylight vision, and show lower light-sensitivity and higher time-resolution than rods that mediate twilight vision. By using purified cones obtained with the method newly developed by us, we searched for the molecular mechanisms that induce the above differences between rods and cones. We found that the extremely high phosphorylation activity on cone visual pigment is one of the key reactions responsible for the higher time resolution in cones.

86	Kitajima, K. 1; Zheng, J. 2; Yen, H. 1; Sugiyama, D. 2; Nakano, T. 2 1 (Graduate School of Medicine) *2 (Graduate School of Frontier Biosciences) Multipotential Differentiation Ability of GATA-1-null Erythroid-Committed Cells Genes & Development, 20, 654-659 (2006) The transcription factor GATA-1 has been believed to be indispensable for the survival of proerythroblasts. However, we found that GATA-1-null proerythroblasts could survive and proliferate on OP9 stroma cells with erythropoietin. Furthermore, myeloid cells were induced from GATA-1-null proerythroblasts by stimulation of myeloid cytokines. Thus, without the transcription factor required for terminal differentiation, even relatively mature and committed cells proliferate continuously with multipotential differentiation ability. Our data suggest that GATA-1 is critical to fix erythroid progenitors to the erythroid lineage.

87	Tashima, Y. ; Taguchi, R.; Murata, C.; Ashida, H.; Kinoshita, T.; Maeda, Y. (Research Institute for Microbial Diseases) PGAP2 Is Essential for Correct Processing and Stable Expression of GPI-anchored Proteins Molecular Biology of the Cell, 17, 1410-1420 (2006) Glycosylphosphatidylinositol (GPI) serves as an anchor to tether proteins to plasma membrane and as a sorting signal for the integration of GPI-anchored proteins (GPI-APs) into rafts. Saturated lipid moieties of GPI-APs are produced by fatty acid remodeling during the transport of GPI-APs and considered an important determinant for the sorting. This paper reports on the first identification of protein involved in fatty acid remodeling of GPI-APs, which was a Golgi/ER resident protein identified by expression cloning and designated PGAP2.

88	Wang, X.; Inoue, S.; Gu, J.; Miyoshi, E. ; Noda, K.; Li, W.; Mizuno-Horikawa, Y.; Nakano, M.; Asahi, M. ; Takahashi, M.; Uozumi, N.; Lee, S. H. ; Ikeda, Y.; Yamaguchi, Y.; Aze, Y.; Tomiyama, Y.; Fujii, J.; Suzuki, K.; Kondo, A. ; Shapiro, S. D.; Lopez-Otin, C.; Kuwaki, T.; Okabe, M.; Honke, K.; Taniguchi, N. (Graduate School of Medicine) Dysregulation of TGF-β1 Receptor Activation Leads to Abnormal Lung Development and Emphysema-like Phenotype in Core Fucose-Deficient Mice Proceedings of the National Academy of Sciences of the United States of America, 102, 15791-15796 (2005)

89	Yoshida, H. 1; Kawane, K. 1,2; Koike, M. 2; Mori, Y.; Uchiyama, Y. 2; Nagata, S. 1,2 1 (Graduate School of Frontier Biosciences) *2 (Graduate School of Medicine) Phosphatidylserine-Dependent Engulfment by Macrophages of Nuclei from Erythroid Precursor Cells Nature, 437, 754-758 (2005)

90	Noguchi, N.; Noiri, Y. ; Narimatsu, M.; Ebisu, S. (Graduate School of Dentistry) Identification and Localization of Extraradicular Biofilm-Forming Bacteria Associated with Refractory Endodontic Pathogens Applied and Environmental Microbiology, 71, 8738-8743 (2005) Bacterial biofilms have been found to develop on human root surfaces outside the apical foramen, and be associated with refractory periapical periodontitis. This report showed that Fusobacterium nucleatum, Porphyromonas gingivalis , and Tannellera forsythensis were frequently detected in human extraradicular biofilms, and positive reactions to anti- P. gingivalis , anti- F . nucleatum and anti- T. forsythensis serum were found at specific portions of the biofilm. This is the first report to demonstrate the periodontopathic bacteria such as P. gingivalis, T. forsythensis , and F. nucleatum are associated with extraradicular biofilm formation and refractory periapical periodontitis.

91	Saito, T.; Okuzaki, D.; Nojima, H. (Research Institute for Microbial Diseases) Mcp5, a Meiotic Cell Cortex Protein, Is Required for Nuclear Movement Mediated by Dynein and Microtubules in Fission Yeast The Journal of Cell Biology, 173, 27-33 (2006) During meiotic prophase I of the fission yeast, oscillatory nuclear movement occurs. This promotes homologous chromosome pairing and recombination and involves cortical dynein, which plays a pivotal role by generating a pulling force with the help of an unknown dynein anchor. Here we show that Mcp5, the homolog of the budding yeast dynein anchor Num1, may be this putative dynein anchor. Our results suggest that PH and coild-coil domains are required for cortical localization and function of Mcp5.

92	Isotani, A. ; Nakanishi, T.; Kobayashi, S. ; Lee, J.; Chuma, S.; Nakatsuji, N.; Ishino, F.; Okabe, M. (Research Institute for Microbial Diseases) Genomic Imprinting of XX Spermatogonia and XX Oocytes Recovered from XX ←→ XY Chimeric Testes Proceedings of the National Academy of Sciences of the United States of America, 102, 4039-4044 (2005)

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