Biology

75	Atarashi, K. ^1 ; Nishimura, J. ^1 ; Shima, T.; Umesaki, Y.; Yamamoto, M. ^{1, 2} ; Onoue, M.; Yagita, H.; Ishii, N.; Evans, R.; Honda, K. ^{1, 2} ; Takeda, K. ^{1, 2} ^1 (Graduate School of Medicine) ^*2 (Immunology Frontier Research Center) ATP Drives LaminaPropria TH17 Cell Differentiation Nature, 455, 808-812 (2008)

76	Hata, K.; Kaibuchi, K.; Inagaki, S.; Yamashita, T. (Graduate School of Medicine) Unc5B Associates with LARG to Mediate the Action of Repulsive Guidance Molecule The Journal of Cell Biology, 184(5), 737-750 (2009) The repulsive guidance molecule RGMa was originally identified as an axon repellent in the visual system. However, the precise intracellular signals are poorly understood. Here, we show that Unc5B, a member of the netrin receptor family, interacts with neogenin as a co-receptor for RGMa. Moreover, leukemia-associated Rho guanine nucleotide-exchange factor (LARG) associates with Unc5B to transduce the RhoA signal. Focal adhesion kinase (FAK) is involved in RGMa-induced tyrosine-phosphorylation of LARG as well as RhoA activation. These findings uncover the molecular basis for diverse functions mediated by RGMa.

77	Hata, K.; Nishimura, R.; Muramatsu, S.; Matsuda, A.; Matsubara, T.; Amano, K.; Ikeda, F.; Harley, V. R.; Yonada, T. (Graduate School of Dentistry) Paraspeckle Protein p54 ^nrb Links Sox9-mediated Transcription with RNA Processing during Chondrogenesis in Mice The Journal of Clinical Investigation, 118(9), 3098-3108 (2008)

78	Hayashi, M. T.; Takahashi T. S.; Nakagawa, T.; Nakayama, J.; Masukata, H. (Graduate School of Science) The Heterochromatin Protein Swi6/HP1 Activates Replication Origins at the Pericentromeric Region and Silent Mating-type Locus Nature Cell Biology, 11, 357-362 (2009)

79	Hishida, T.; Kubota, Y.; Carr, A. M.; Iwasaki, H. (Research Institute for Microbial Deseases) RAD6-RAD18-RAD5 pathway-dependent Tolerance to Chronic Low-dose UV Light Nature, 457(29), 612-616 (2009) In nature, organisms are exposed to chronic low-dose UV (CLUV) as opposed to the acute high doses common to laboratory experiments. Here, we have explored the biological effects of CLUV irradiation, utilizing budding yeast as a model organism and identify a key role for the RAD6 damage tolerance pathway in promoting DNA replication of damaged templates. We propose that RAD6 pathway is specifically important during CLUV exposure to prevent counter-productive checkpoint activation and allow cells to proliferate normally.

80	Hitomi, K.; DiTacchio, L.; Arvai, A. S.; Yamamoto, J.; Kim, S.-T.; Todo, T.; Tainer, J. A.; Iwai, S.; Panda, S.; Getzoff, E. D. (Graduate School of Engineering Science) Functional Motifs in the (6-4) Photolyase Crystal Structure Make a Comparative Framework for DNA Repair Photolyases and Clock Cryptochromes Proceedings of the National Academy of Sciences of the United States of America, 106, 6962-6967 (2009) Homologous flavoproteins from the photolyase (PHR)/cryptochrome (CRY) family use the FAD cofactor in PHRs to catalyze DNA repair and in CRYs to tune the circadian clock and control development. To help address how PHR/CRY members achieve these diverse functions, we determined the crystallographic structure of Arabidopsis thaliana (6-4) PHR, which is strikingly similar in sequence to human circadian clock CRYs. Mutational analyses were combined with this prototypic structure for the (6-4) PHR/clock CRY cluster to identify structural and functional motifs.

81	Ito, Y. ^1 ; Toyota, H. ^2 ; Kaneko, K.; Yomo, T. ^{1, 3} ^1 (Graduate School of Information Science and Technology) ^2 (Graduate School of Engineering) ^3 (Graduate School of Frontier Biosciences) How Selection Affects Phenotypic Fluctuation Molecular Systems Biology, 5, 264 (2009) Phenotypic fluctuation among cells possessing identical genes is quite large. Because the fluctuation is highly relevant to essential biological events, it is crucial to understand how the fluctuation is produced. Here we demonstrated that the fluctuation can be produced over the course of evolution by carrying out cycles of mutation and selection using bacteria cells expressing green fluorescent protein (GFP). Under the severe selective environment where only a small fraction of cells survives, increasing phenotypic fluctuation is advantageous for survival of cells.

82	Kasai, A. ^1 ; Shintani, N. ^1 ; Kato, H. ^1 ; Matsuda, S. ^2 ; Gomi, F. ^2 ; Haba, R. ^1 ; Hashimoto, H. ^{1, 2} ; Kakuda, M. ^2 ; Tano, Y. ^2 ; Baba, A. ^1 ^1 (Graduate School of Pharmaceutical Sciences) ^2 (Graduate School of Medicine) Retardation of Retinal Vascular Development in Apelin-Deficient Mice Arteriosclerosis, Thrombosis and Vascular Biology, 28, 1717-1722 (2008) We examined the phenotype of mice lacking apelin, an endogenous ligand for orphan G protein-coupled receptor APJ. The mutant showed impaired retinal vascularization in the early postnatal period, when the retinal apelin/APJ mRNAs were markedly upregulated. In the mutant, angiogenic responses to VEGF and FGF2 were remarkably decreased, which were partially restored by apelin. These data suggest that apelin/APJ signaling contributes to the pathogenesis of retinal neovascularization in ocular diseases such as diabetic retinopathy and retinopathy of prematurity in a cooperative manner with classical angiogenic factors.

83	Kosaka, H.; Shinohara, M.; Shinohara, A. (Institute for Protein Research) Csm4-dependent Telomere Movement on Nuclear Envelope Promotes Meiotic Recombination PLoS Genetics, 4(9), e1000196-1-12 (2008) During meiotic prophase, chromosomes display rapid movement, and their telomeres attach to the nuclear envelope and cluster to form a “chromosomal bouquet.” In budding yeast, telomere clustering is promoted by a meiosis-specific telomere-binding protein, Ndj1. Here we show that a meiosis-specific protein, Csm4, which forms a complex with Ndj1, facilitates bouquet formation. We propose that chromosome movement and associated telomere dynamics at the nuclear envelope promotes the completion of key biochemical steps during meiotic recombination.

84	Maeda, S.; Nakagawa, S.; Suga, M.; Yamashita, E.; Oshima, A.; Fujiyoshi, Y.; Tsukihara, T. (Institute for Protain Research) Structure of the Connexin 26 Gap Junction Channel at 3.5 Å Resolution Nature, 458(2), 597-602 (2009)

85 86 87	Maeda, Y. ^{1, 2} ; Ide, T. ^3 ; Koike, M. ^4 ; Uchiyama, Y. ^4 ; Kinoshita, T. ^{1, 2} ^1 (Research Institute for Microbial Diseases) ^2 (Immunology Frontier Research Center) ^3 (Graduate School of Frontier Biosciences) ^4 (Graduate School of Medicine) GPHR is a Novel Anion Channel Critical for Acidification and Functions of the Golgi Apparatus Nature Cell Biology, 10(10), 1135-1145 (2008) Manabe, R.; Tsutsui, K.; Yamada, T.; Kimura, M.; Nakano, I.; Shimono, C.; Sanzen, N.; Furutani, Y.; Fukuda, T.; Oguri, Y.; Shimamoto, K.; Kiyozumi, D.; Sato, Y.; Sado, Y.; Senoo, H.; Yamashita, S.; Fukuda, S.; Kawai, J.; Sugiura, N.; Kimata,K.; Hayashizaki, Y.; Sekiguchi, K. (Institute for Protain Reseach) Transcriptome-Based Systematic Identification of Extracellular Matrix Proteins Proceedings of the National Academy of Sciences of the United States of America, 105(35), 12849-12854 (2008) We developed a strategy for transcriptome-wide identification of novel extracellular matrix (ECM) proteins based on computational screening of > 60,000 RIKEN’s mouse cDNAs for secreted proteins, followed by in vitro assays for ECM-assembling activities, interactions with other ECM molecules, modifications with glycosaminoglycans, and cell-adhesive activities. These in vitro assays were then complemented with immunohistochemical analysis. We identified 16 novel ECM proteins, of which seven were localized in basement membranes (BMs). We also constructed a “body-map” of BM proteins, the first comprehensive immunohistochemistry-based expression profiles of BM proteins. Matsunaga, K. ^1 ; Saitoh, T. ^{1, 2} ; Tabata, K. ^1 ; Omori, H. ^1 ; Satoh, T. ^{1, 2} ; Kurotori, N. ^1 ; Maejima, I. ^1 ; Shirahama-Noda, K. ^1 ; Ichimura, T.; Isobe, T.; Akira, S. ^{1, 2} ; Noda, T. ^1 ; Yoshimori, T. ^1 ^1 (Research Institute for Microbial Deseases) ^2 (Immunology Frontier Research Center) Two Beclin 1-binding Proteins, Atg14L and Rubicon, Reciprocally Regulate Autophagy at Different Stages Nature Cell Biology, 11(4), 385-396 (2009)

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