2022/11/29 更新

写真a

フルカワ ケンタロウ
古川 健太郎
FURUKAWA Kentaro
所属
教育研究院 医歯学系 特任助教
医歯学総合研究科 特任助教
職名
特任助教
外部リンク

学位

  • 博士(農学) ( 2005年3月   東北大学 )

研究キーワード

  • 酵母

  • マイトファジー

  • オートファジー

  • ミトコンドリア

研究分野

  • ライフサイエンス / 機能生物化学

  • ライフサイエンス / 細胞生物学

経歴(researchmap)

  • 新潟大学   Graduate School of Medical and Dental Sciences   医学部准教授

    2021年9月 - 現在

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  • 新潟大学 大学院医歯学総合研究科   機能制御学分野   特任助教

    2015年2月 - 現在

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  • ヨーテボリ大学   上級研究員

    2009年11月 - 2014年12月

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  • ヨーテボリ大学   ポスドク研究員

    2006年5月 - 2009年10月

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  • 東北大学 大学院農学研究科 応用生命科学専攻 日本学術振興会特別研究員   Graduate School of Agricultural Science, Division of Life Science   (PD)

    2005年4月 - 2006年3月

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  • 東北大学 大学院農学研究科 応用生命科学専攻   Graduate School of Agricultural Science, Division of Life Science   日本学術振興会特別研究員 (DC2)

    2004年4月 - 2005年3月

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▶ 全件表示

経歴

  • 新潟大学   医歯学総合研究科   特任助教

    2020年11月 - 現在

  • 新潟大学   医歯学総合研究科   特任助教

    2015年2月 - 2020年10月

学歴

  • 東北大学 大学院農学研究科 応用生命科学専攻 博士課程   Graduate School of Agricultural Science   Division of Life Science

    2002年4月 - 2005年3月

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  • 東北大学 大学院農学研究科 応用生命科学専攻 修士課程   Graduate School of Agricultural Science   Division of Life Science

    2000年4月 - 2002年3月

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  • 東北大学 農学部 応用生物化学科   Faculty of Agriculture   Department of Applied Biological Chemistry

    1996年4月 - 2000年3月

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所属学協会

 

論文

  • Downregulation of the ypdA gene encoding an intermediate of His-Asp phosphorelay signaling in Aspergillus nidulans induces the same cellular effects as the phenylpyrrole fungicide fludioxonil. 査読

    Akira Yoshimi, Daisuke Hagiwara, Miyako Ono, Yasuyuki Fukuma, Yura Midorikawa, Kentaro Furukawa, Tomonori Fujioka, Osamu Mizutani, Natsuko Sato, Ken Miyazawa, Jun-Ichi Maruyama, Junichiro Marui, Youhei Yamagata, Tasuku Nakajima, Chihiro Tanaka, Keietsu Abe

    Frontiers in Fungal Biology   2021年7月

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  • Mitophagy reporter mouse analysis reveals increased mitophagy activity in disuse-induced muscle atrophy 査読 国際誌

    Shun-Ichi Yamashita, Masanao Kyuuma, Keiichi Inoue, Yuki Hata, Ryu Kawada, Masaki Yamabi, Yasuyuki Fujii, Junko Sakagami, Tomoyuki Fukuda, Kentaro Furukawa, Satoshi Tsukamoto, Tomotake Kanki

    Journal of Cellular Physiology   2021年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/jcp.30404

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  • Mitophagy regulation mediated by the Far complex in yeast. 査読 国際誌

    Kentaro Furukawa, Aleksei Innokentev, Tomotake Kanki

    Autophagy   17 ( 4 )   1042 - 1043   2021年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Mitochondrial autophagy (mitophagy) selectively degrades mitochondria and plays an important role in mitochondrial homeostasis. In the yeast Saccharomyces cerevisiae, the phosphorylation of the mitophagy receptor Atg32 by casein kinase 2 is essential for mitophagy, whereas this phosphorylation is counteracted by the protein phosphatase Ppg1. Although Ppg1 functions cooperatively with the Far complex (Far3, Far7, Far8, Vps64/Far9, Far10 and Far11), their relationship and the underlying phosphoregulatory mechanism of Atg32 remain unclear. Our recent study revealed: (i) the Far complex plays its localization-dependent roles, regulation of mitophagy and target of rapamycin complex 2 (TORC2) signaling, via the mitochondria- and endoplasmic reticulum (ER)-localized Far complexes, respectively; (ii) Ppg1 and Far11 form a subcomplex, and Ppg1 activity is required to assemble the sub- and core-Far complexes; (iii) association and dissociation between the Far complex and Atg32 are crucial determinants for mitophagy regulation. Here, we summarize our findings and discuss unsolved issues.

    DOI: 10.1080/15548627.2021.1885184

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  • Association and dissociation between the mitochondrial Far complex and Atg32 regulate mitophagy. 査読 国際誌

    Aleksei Innokentev, Kentaro Furukawa, Tomoyuki Fukuda, Tetsu Saigusa, Keiichi Inoue, Shun-Ichi Yamashita, Tomotake Kanki

    eLife   9   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Mitophagy plays an important role in mitochondrial homeostasis. In yeast, the phosphorylation of the mitophagy receptor Atg32 by casein kinase 2 is essential for mitophagy. This phosphorylation is counteracted by the yeast equivalent of the STRIPAK complex consisting of the PP2A-like protein phosphatase Ppg1 and Far3-7-8-9-10-11 (Far complex), but the underlying mechanism remains elusive. Here we show that two subpopulations of the Far complex reside in the mitochondria and endoplasmic reticulum, respectively, and play distinct roles; the former inhibits mitophagy via Atg32 dephosphorylation, and the latter regulates TORC2 signaling. Ppg1 and Far11 form a subcomplex, and Ppg1 activity is required for the assembling integrity of Ppg1-Far11-Far8. The Far complex preferentially interacts with phosphorylated Atg32, and this interaction is weakened by mitophagy induction. Furthermore, the artificial tethering of Far8 to Atg32 prevents mitophagy. Taken together, the Ppg1-mediated Far complex formation and its dissociation from Atg32 are crucial for mitophagy regulation.

    DOI: 10.7554/eLife.63694

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  • Atg43 tethers isolation membranes to mitochondria to promote starvation-induced mitophagy in fission yeast. 査読 国際誌

    Tomoyuki Fukuda, Yuki Ebi, Tetsu Saigusa, Kentaro Furukawa, Shun-Ichi Yamashita, Keiichi Inoue, Daiki Kobayashi, Yutaka Yoshida, Tomotake Kanki

    eLife   9   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Degradation of mitochondria through mitophagy contributes to the maintenance of mitochondrial function. In this study, we identified that Atg43, a mitochondrial outer membrane protein, serves as a mitophagy receptor in the model organism Schizosaccharomyces pombe to promote the selective degradation of mitochondria. Atg43 contains an Atg8-family-interacting motif essential for mitophagy. Forced recruitment of Atg8 to mitochondria restores mitophagy in Atg43-deficient cells, suggesting that Atg43 tethers expanding isolation membranes to mitochondria. We found that the mitochondrial import factors, including the Mim1-Mim2 complex and Tom70, are crucial for mitophagy. Artificial mitochondrial loading of Atg43 bypasses the requirement of the import factors, suggesting that they contribute to mitophagy through Atg43. Atg43 not only maintains growth ability during starvation but also facilitates vegetative growth through its mitophagy-independent function. Thus, Atg43 is a useful model to study the mechanism and physiological roles, as well as the origin and evolution, of mitophagy in eukaryotes.

    DOI: 10.7554/eLife.61245

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  • Regulatory Mechanisms of Mitochondrial Autophagy: Lessons From Yeast. 査読 国際誌

    Kentaro Furukawa, Aleksei Innokentev, Tomotake Kanki

    Frontiers in plant science   10   1479 - 1479   2019年

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    記述言語:英語  

    Mitochondria produce the majority of ATP required by cells via oxidative phosphorylation. Therefore, regulation of mitochondrial quality and quantity is important for maintaining cellular activities. Mitophagy, the selective degradation of mitochondria, is thought to contribute to control of mitochondrial quality and quantity. In recent years, the molecular mechanism of mitophagy has been extensively studied in yeast and mammalian cells. In particular, identification of the mitophagy receptor Atg32 has contributed to substantial progress in understanding of mitophagy in yeast. This review summarizes the molecular mechanism of mitophagy in yeast and compares it to the mechanism of mitophagy in mammals. We also discuss the current understanding of mitophagy in plants.

    DOI: 10.3389/fpls.2019.01479

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  • The PP2A-like Protein Phosphatase Ppg1 and the Far Complex Cooperatively Counteract CK2-Mediated Phosphorylation of Atg32 to Inhibit Mitophagy 査読

    Kentaro Furukawa, Tomoyuki Fukuda, Shun-ichi Yamashita, Tetsu Saigusa, Yusuke Kurihara, Yutaka Yoshida, Hiromi Kirisako, Hitoshi Nakatogawa, Tomotake Kanki

    Cell Reports   23 ( 12 )   3579 - 3590   2018年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier B.V.  

    Mitophagy plays an important role in mitochondrial quality control. In yeast, phosphorylation of the mitophagy receptor Atg32 by casein kinase 2 (CK2) upon induction of mitophagy is a prerequisite for interaction of Atg32 with Atg11 (an adaptor protein for selective autophagy) and following delivery of mitochondria to the vacuole for degradation. Because CK2 is constitutively active, Atg32 phosphorylation must be precisely regulated to prevent unrequired mitophagy. We found that the PP2A (protein phosphatase 2A)-like protein phosphatase Ppg1 was essential for dephosphorylation of Atg32 and inhibited mitophagy. We identified the Far complex proteins, Far3, Far7, Far8, Far9, Far10, and Far11, as Ppg1-binding proteins. Deletion of Ppg1 or Far proteins accelerated mitophagy. Deletion of a cytoplasmic region (amino acid residues 151–200) of Atg32 caused the same phenotypes as in ppg1Δ cells, which suggested that dephosphorylation of Atg32 by Ppg1 required this region. Therefore, Ppg1 and the Far complex cooperatively dephosphorylate Atg32 to prevent excessive mitophagy. Mitophagy in yeast is initiated by CK2-mediated phosphorylation of the mitophagy receptor Atg32. However, how this phosphorylation is prevented under non-mitophagy-inducing conditions is unclear. Furukawa et al. show that the PP2A-like protein phosphatase Ppg1 and the Far complex negatively regulate mitophagy by counteracting CK2-mediated phosphorylation of Atg32.

    DOI: 10.1016/j.celrep.2018.05.064

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  • Mitophagy in yeast: A screen of mitophagy-deficient mutants. 査読

    Furukawa K, Kanki T

    Methods in Molecular Biology   1759   95 - 104   2018年

  • PP2A-like protein phosphatase Ppg1: an emerging negative regulator of mitophagy in yeast. 査読

    Furukawa K, Kanki T

    Autophagy   14 ( 12 )   2171 - 2172   2018年

  • Mitochondrial division occurs concurrently with autophagosome formation but independently of Drp1 during mitophagy 査読

    Shun-ichi Yamashita, Xiulian Jin, Kentaro Furukawa, Maho Hamasaki, Akiko Nezu, Hidenori Otera, Tetsu Saigusa, Tamotsu Yoshimori, Yasuyoshi Sakai, Katsuyoshi Mihara, Tomotake Kanki

    JOURNAL OF CELL BIOLOGY   215 ( 5 )   649 - 665   2016年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ROCKEFELLER UNIV PRESS  

    Mitophagy is thought to play an important role in mitochondrial quality control. Mitochondrial division is believed to occur first, and autophagosome formation subsequently occurs to enwrap mitochondria as a process of mitophagy. However, there has not been any temporal analysis of mitochondrial division and autophagosome formation in mitophagy. Therefore, the relationships among these processes remain unclear. We show that the mitochondrial division factor Dnm1 in yeast or Drp1 in mammalian cells is dispensable for mitophagy. Autophagosome formation factors, such as FIP200, ATG14, and WIPIs, were essential for the mitochondrial division for mitophagy. Live-cell imaging showed that isolation membranes formed on the mitochondria. A small portion of the mitochondria then divided from parental mitochondria simultaneously with the extension of isolation membranes and autophagosome formation. These findings suggest the presence of a mitophagy process in which mitochondrial division for mitophagy is accomplished together with autophagosome formation.

    DOI: 10.1083/jcb.201605093

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  • Mitophagy in yeast: Molecular mechanisms and physiological role. 査読

    Kanki T, Furukawa K, Yamashita S

    Biochimica et Biophysica Acta   1853 ( 10 Pt B )   2756 - 2765   2015年10月

  • A fungicide-responsive kinase as a tool for synthetic cell fate regulation 査読

    Kentaro Furukawa, Stefan Hohmann

    NUCLEIC ACIDS RESEARCH   43 ( 14 )   7162 - 7170   2015年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Engineered biological systems that precisely execute defined tasks have major potential for medicine and biotechnology. For instance, gene-or cell-based therapies targeting pathogenic cells may replace time-and resource-intensive drug development. Engineering signal transduction systems is a promising, yet presently underexplored approach. Here, we exploit a fungicide-responsive heterologous histidine kinase for pathway engineering and synthetic cell fate regulation in the budding yeast Saccharomyces cerevisiae. Rewiring the osmoregulatory Hog1 MAPK signalling system generates yeast cells programmed to execute three different tasks. First, a synthetic negative feedback loop implemented by employing the fungicide-responsive kinase and a fungicide-resistant derivative reshapes the Hog1 activation profile, demonstrating how signalling dynamics can be engineered. Second, combinatorial integration of different genetic parts including the histidine kinases, a pathway activator and chemically regulated promoters enables control of yeast growth and/or gene expression in a two-input Boolean logic manner. Finally, we implemented a genetic 'suicide attack' system, in which engineered cells eliminate target cells and themselves in a specific and controllable manner. Taken together, fungicide-responsive kinases can be applied in different constellations to engineer signalling behaviour. Sensitizing engineered cells to existing chemicals may be generally useful for future medical and biotechnological applications.

    DOI: 10.1093/nar/gkv678

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  • Differential Role of HAMP-like Linkers in Regulating the Functionality of the Group III Histidine Kinase DhNik1p 査読

    Harsimran Kaur, Shikha Singh, Yogendra S. Rathore, Anupam Sharma, Kentaro Furukawa, Stefan Hohmann, Ashish, Alok K. Mondal

    JOURNAL OF BIOLOGICAL CHEMISTRY   289 ( 29 )   20245 - 20258   2014年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    Nik1 orthologs are sensor kinases that function upstream of the high osmolarity glycerol/p38 MAPK pathway in fungi. They contain a poly-HAMP module at their N terminus, which plays a pivotal role in osmosensing as well as fungal death upon exposure to fludioxonil. DhNik1p is a typical member of this class that contains five HAMP domains and four HAMP-like linkers. We investigated the contribution of each of the HAMP-like linker regions to the functionality of DhNik1p and found that the HAMP4b linker was essential as its deletion resulted in the complete loss of activity. Replacement of this linker with flexible peptide sequences did not restore DhNik1p activity. Thus, the HAMP-like sequence and possibly structural features of this linker region are indispensable for the kinase activity of DhNik1p. To gain insight into the global shape of the poly-HAMP module in DhNik1p (HAMP1-5), multi-angle laser light and small angle x-ray scattering studies were carried out. Those data demonstrate that the maltose-binding protein-tagged HAMP1-5 protein exist as a dimer in solution with an elongated shape of maximum linear dimension similar to 365 angstrom. Placement of a sequence similarity based model of the HAMP1-5 protein inside experimental data-based models showed how two chains of HAMP1-5 are entwined on each other and the overall structure retained a periodicity. Normal mode analysis of the structural model is consistent with the H4b linker being a key to native-like collective motion in the protein. Overall, our shape-function studies reveal how different elements in the HAMP1-5 structure mediate its function.

    DOI: 10.1074/jbc.M114.554303

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  • Rewiring yeast osmostress signalling through the MAPK network reveals essential and non-essential roles of Hog 1 in osmoadaptation 査読

    Roja Babazadeh, Takako Furukawa, Stefan Hohmann, Kentaro Furukawa

    SCIENTIFIC REPORTS   4   4697   2014年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Mitogen-activated protein kinases (MAPKs) have a number of targets which they regulate at transcriptional and post-translational levels to mediate specific responses. The yeast Hog1 MAPK is essential for cell survival under hyperosmotic conditions and it plays multiple roles in gene expression, metabolic regulation, signal fidelity and cell cycle regulation. Here we describe essential and non-essential roles of Hog1 using engineered yeast cells in which osmoadaptation was reconstituted in a Hog1-independent manner. We rewired Hog1-dependent osmotic stress-induced gene expression under the control of Fus3/Kss1 MAPKs, which are activated upon osmostress via crosstalk in hog1 Delta cells. This approach revealed that osmotic up-regulation of only two Hog1-dependent glycerol biosynthesis genes, GPD1 and GPP2, is sufficient for successful osmoadaptation. Moreover, some of the previously described Hog1-dependent mechanisms appeared to be dispensable for osmoadaptation in the engineered cells. These results suggest that the number of essential MAPK functions may be significantly smaller than anticipated and that knockout approaches may lead to over-interpretation of phenotypic data.

    DOI: 10.1038/srep04697

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  • Synthetic biology: lessons from engineering yeast MAPK signalling pathways 査読

    Kentaro Furukawa, Stefan Hohmann

    MOLECULAR MICROBIOLOGY   88 ( 1 )   5 - 19   2013年4月

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    記述言語:英語   出版者・発行元:WILEY  

    All living cells respond to external stimuli and execute specific physiological responses through signal transduction pathways. Understanding the mechanisms controlling signalling pathways is important for diagnosing and treating diseases and for reprogramming cells with desired functions. Although many of the signalling components in the budding yeast Saccharomyces cerevisiae have been identified by genetic studies, many features concerning the dynamic control of pathway activity, cross-talk, cell-to-cell variability or robustness against perturbation are still incompletely understood. Comparing the behaviour of engineered and natural signalling pathways offers insight complementary to that achievable with standard genetic and molecular studies. Here, we review studies that aim at a deeper understanding of signalling design principles and generation of novel signalling properties by engineering the yeast mitogen-activated protein kinase (MAPK) pathways. The underlying approaches can be applied to other organisms including mammalian cells and offer opportunities for building synthetic pathways and functionalities useful in medicine and biotechnology.

    DOI: 10.1111/mmi.12174

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  • Fungal fludioxonil sensitivity is diminished by a constitutively active form of the group III histidine kinase 査読

    Kentaro Furukawa, Anmoldeep Randhawa, Harsimran Kaur, Alok K. Mondal, Stefan Hohmann

    FEBS LETTERS   586 ( 16 )   2417 - 2422   2012年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    The fungicide fludioxonil is used to control plant-pathogenic fungi by causing improper activation of the Hog1-type MAPK. However, the appearance of fludioxonil resistant mutants, mostly caused by mutations in the group III histidine kinases, poses a serious problem. Moreover, such mutations cause also hyperosmotic sensitivity and the underlying mechanism has been elusive for a long time. Using Saccharomyces cerevisiae as an experimental host, we show that those phenotypes are conferred by a constitutively active form of the group III histidine kinase. Our results explain the different reasons for fludioxonil resistance conferred by its deletion and missense mutation. (c) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.febslet.2012.05.057

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  • The genome of the xerotolerant mold Wallemia sebi reveals adaptations to osmotic stress and suggests cryptic sexual reproduction 査読

    Mahajabeen Padamsee, T. K. Arun Kumar, Robert Riley, Manfred Binder, Alex Boyd, Ana M. Calvo, Kentaro Furukawa, Cedar Hesse, Stefan Hohmann, Tim Y. James, Kurt LaButti, Alla Lapidus, Erika Lindquist, Susan Lucas, Kari Miller, Sourabha Shantappa, Igor V. Grigoriev, David S. Hibbett, David J. McLaughlin, Joseph W. Spatafora, M. Catherine Aime

    FUNGAL GENETICS AND BIOLOGY   49 ( 3 )   217 - 226   2012年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Wallemia (Wallemiales, Wallemiomycetes) is a genus of xerophilic Fungi of uncertain phylogenetic position within Basidiomycota. Most commonly found as food contaminants, species of Wallemia have also been isolated from hypersaline environments. The ability to tolerate environments with reduced water activity is rare in Basidiomycota. We sequenced the genome of W. sebi in order to understand its adaptations for surviving in osmotically challenging environments, and we performed phylogenomic and ultrastructural analyses to address its systematic placement and reproductive biology. W. sebi has a compact genome (9.8 Mb), with few repeats and the largest fraction of genes with functional domains compared with other Basidiomycota. We applied several approaches to searching for osmotic stress-related proteins. In silico analyses identified 93 putative osmotic stress proteins; homology searches showed the HOG (High Osmolarity Glycerol) pathway to be mostly conserved. Despite the seemingly reduced genome, several gene family expansions and a high number of transporters (549) were found that also provide clues to the ability of W. sebi to colonize harsh environments. Phylogenetic analyses of a 71-protein dataset support the position of Wallemia as the earliest diverging lineage of Agaricomycotina, which is confirmed by septal pore ultrastructure that shows the septal pore apparatus as a variant of the Tremella-type. Mating type gene homologs were identified although we found no evidence of meiosis during conidiogenesis, suggesting there may be aspects of the life cycle of W. sebi that remain cryptic. (C) 2012 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.fgb.2012.01.007

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  • Efficient Construction of Homozygous Diploid Strains Identifies Genes Required for the Hyper-Filamentous Phenotype in Saccharomyces cerevisiae 査読

    Kentaro Furukawa, Takako Furukawa, Stefan Hohmann

    PLOS ONE   6 ( 10 )   e26584   2011年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Yeast cells undergo diploid-specific developments such as spore formation via meiosis and pseudohyphal development under certain nutrient-limited conditions. Studies on these aspects require homozygous diploid mutants, which are generally constructed by crossing strains of opposite mating-type with the same genetic mutation. So far, there has been no direct way to generate and select diploids from haploid cells. Here, we developed a method for efficient construction of homozygous diploids using a PGAL1-HO gene (galactose-inducible mating-type switch) and a PSTE18-URA3 gene (counter selection marker for diploids). Diploids are generated by transient induction of the HO endonuclease, which is followed by mating of part of the haploid population. Since the STE18 promoter is repressed in diploids, diploids carrying PSTE18-URA3 can be selected on 5-fluoroorotic acid (5-FOA) plates where the uracil prototrophic haploids cannot grow. To demonstrate that this method is useful for genetic studies, we screened suppressor mutations of the complex colony morphology, strong agar invasion and/or hyper-filamentous growth caused by lack of the Hog1 MAPK in the diploid Sigma 1278b strain background. Following this approach, we identified 49 suppressor mutations. Those include well-known positive regulator genes for filamentous growth signaling pathways, genes involved in mitochondrial function, DNA damage checkpoint, chromatin remodeling, and cell cycle, and also previously uncharacterized genes. Our results indicate that combinatorial use of the PGAL1-HO and PSTE18-URA3 genes is suitable to efficiently construct and select diploids and that this approach is useful for genetic studies especially when combined with large-scale screening.

    DOI: 10.1371/journal.pone.0026584

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  • Distributed biological computation with multicellular engineered networks 査読

    Sergi Regot, Javier Macia, Nuria Conde, Kentaro Furukawa, Jimmy Kjellen, Tom Peeters, Stefan Hohmann, Eulalia de Nadal, Francesc Posas, Ricard Sole

    NATURE   469 ( 7329 )   207 - 211   2011年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Ongoing efforts within synthetic and systems biology have been directed towards the building of artificial computational devices(1) using engineered biological units as basic building blocks(2,3). Such efforts, inspired in the standard design of electronic circuits(4-7), are limited by the difficulties arising from wiring the basic computational units (logic gates) through the appropriate connections, each one to be implemented by a different molecule. Here, we show that there is a logically different form of implementing complex Boolean logic computations that reduces wiring constraints thanks to a redundant distribution of the desired output among engineered cells. A practical implementation is presented using a library of engineered yeast cells, which can be combined in multiple ways. Each construct defines a logic function and combining cells and their connections allow building more complex synthetic devices. As a proof of principle, we have implemented many logic functions by using just a few engineered cells. Of note, small modifications and combination of those cells allowed for implementing more complex circuits such as a multiplexer or a 1-bit adder with carry, showing the great potential for re-utilization of small parts of the circuit. Our results support the approach of using cellular consortia as an efficient way of engineering complex tasks not easily solvable using single-cell implementations.

    DOI: 10.1038/nature09679

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  • Expression of the yeast aquaporin Aqy2 affects cell surface properties under the control of osmoregulatory and morphogenic signalling pathways 査読

    Kentaro Furukawa, Frederic Sidoux-Walter, Stefan Hohmann

    MOLECULAR MICROBIOLOGY   74 ( 5 )   1272 - 1286   2009年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    P>Aquaporins mediate rapid and selective water transport across biological membranes. The yeast Saccharomyces cerevisiae possesses two aquaporins, Aqy1 and Aqy2. Here, we show that Aqy2 is involved in controlling cell surface properties and that its expression is controlled by osmoregulatory and morphogenic signalling pathways. Deletion of AQY2 results in diminished fluffy colony morphology while overexpression of AQY2 causes strong agar invasion and adherence to plastic surfaces. Hyper-osmotic stress inhibits morphological developments including the above characteristics as well as AQY2 expression through the osmoregulatory Hog1 mitogen-activated protein kinase. Moreover, two pathways known to control morphological developments are involved in regulation of AQY2 expression: the protein kinase A pathway derepresses AQY2 expression through the Sfl1 repressor, and the filamentous growth Kss1 mitogen-activated protein kinase pathway represses AQY2 expression in a Kss1 activity-independent manner. The AQY2 expression pattern resembles in many ways that of MUC1/FLO11, which encodes a cell surface glycoprotein required for morphological developments. Our observations suggest a potential link between aquaporins and cell surface properties, and relate to the proposed role of mammalian aquaporins in tumour cell migration and invasion.

    DOI: 10.1111/j.1365-2958.2009.06933.x

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  • Alternative Processing of Proproteins in Aspergilli kexB Gene Disruptants under Hyperosmotic Conditions 査読

    Osamu Mizutani, Kentaro Furukawa, Shunsuke Ichiyanagi, Yoshihiko Matsuda, Masafumi Tokuoka, Tomonori Fujka, Youhei Yamagata, Katsuya Gomi, Keietsu Abe

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   73 ( 1 )   40 - 46   2009年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    Disruption of the kexB gene encoding a subtilisin-like processing protease in Aspergillus oryzae and Aspergillus nidulans led to remarkable morphological defects, and these phenotypes were suppressed under hyperosmotic conditions. In this study, we investigated to determine whether non-KexB proteases might complement the in vivo function of KexB in the two Aspergillus kexB disruptants. Neither overexpression of opsA or opsB encoding A. oryzae aspartyl proteases homologous to yeast yapsins (YPS1/2) suppressed the kexB mutation, although yapsins are multicopy suppressors for the yeast kex2 mutation. A. nidulans and A. oryzae kexB disruptants grown under hyperosmotic conditions processed a recombinant fusion protein carrying a synthetic dibasic processing site (Lys-Arg) although the disruptants grown under normal growth conditions did not cleave the site. These results suggest that the two Aspergilli have other potential processing proteases that are induced and/or activated under hyperosmotic conditions and consequently complement, at least in part, the in vivo function of KexB.

    DOI: 10.1271/bbb.80437

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  • MpkA-dependent and -independent cell wall integrity signaling in Aspergillus nidulans 査読

    Tomonori Fujioka, Osamu Mizutani, Kentaro Furukawa, Natsuko Sato, Akira Yoshimi, Youhei Yamagata, Tasuku Nakajima, Keietsu Abe

    EUKARYOTIC CELL   6 ( 8 )   1497 - 1510   2007年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    Cell wall integrity signaling (CWIS) maintains cell wall biogenesis in fungi, but only a few transcription factors (TFs) and target genes downstream of the CWIS cascade in filamentous fungi are known. Because a mitogen-activated protein kinase (MpkA) is a key CWIS enzyme, the transcriptional regulation of mpkA and of cell wall-related genes (CWGs) is important in cell wall biogenesis. We cloned Aspergillus nidulans mpkA; rlmA, a TF gene orthologous to Saccharomyces cerevisiae RLM1 that encodes Rlm1p, a major Mpk1p-dependent TF that regulates the transcription of MPK1 besides that of CWGs; and Answi4 and Answi6, homologous to S. cerevisiae SWI4 and SWI6, encoding the Mpk1p-activating TF complex Swi4p-Swi6p, which regulates CWG transcription in a cell cycle-dependent manner. A. nidulans rlmA and mpkA cDNA functionally complemented S. cerevisiae rlm Delta and mpk1 Delta mutants, respectively, but Answi4 and Answi6 cDNA did not complement swi4 Delta and swi6 Delta mutants. We constructed A. nidulans rlmA, Answi4 and Answi6, and mpkA disruptants (rlmA Delta, Answi4 Delta Answi6 Delta, and mpkA Delta strains) and analyzed mpkA and CWG transcripts after treatment with a beta-1,3-glucan synthase inhibitor (micafungin) that could activate MpkA via CWIS. Levels of mpkA transcripts in the mutants as well as those in the wild type were changed after micafungin treatment. The P-glucuronidase reporter gene controlled by the mpkA promoter was expressed in the wild type but not in the mpkA Delta strain. Thus, mpkA transcription seems to be autoregulated by CWIS via MpkA but not by RlmA or AnSwi4-AnSwi6. The transcription of most CWGs except alpha-1,3-glucan synthase genes (agsA and agsB) was independent of RlmA and AnSwi4-AnSwi6 and seemed to be regulated by non-MpkA signaling. The transcriptional regulation of mpkA and of CWGs via CWIS in A. nidulans differs significantly from that in S. cerevisiae.

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  • Novel reporter gene expression systems for monitoring activation of the Aspergillus nidulans HOG pathway 査読

    Kentaro Furukawa, Akira Yoshimi, Takako Furukawa, Yukiko Hoshi, Daisuke Hagiwara, Natsuko Sato, Tomonori Fujioka, Osamu Mizutani, Takeshi Mizuno, Tetsuo Kobayashi, Keietsu Abe

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   71 ( 7 )   1724 - 1730   2007年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    The Aspergillus nidulans high-osmolarity glycerol response (AnHOG) pathway is involved in osmoadaptation. We found that fludioxonil, a fungicide, causes improper activation of HogA mitogen-activated protein kinase (MAPK) in A. nidulans. Here we present novel reporter systems for monitoring activation of the AnHOG pathway. The promoter region of gfdB (glycerol-3-phosphate dehydrogenase), whose expression depends on the presence of HogA, was fused to a beta-glucuronidase uidA gene (GUS) to construct the reporter, which was introduced into A. nidulans wild type and hogA Delta. Increased GUS activity was detected in the wild type only when it was treated with high osmolarity or fludioxonil, while reporter activity was scarcely stimulated in the hogA Delta mutant. These results indicate that the reporter activity is controlled via HogA activation. Furthermore, we present possible applications of the reporter systems in screening new antifungal compounds.

    DOI: 10.1271/bbb.70131

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  • The SskA and SrrA response regulators are implicated in oxidative stress responses of hyphae and asexual spores in the phosphorelay signaling network of Aspergillus nidulans 査読

    Daisuke Hagiwara, Yoshihiro Asano, Junichiro Marui, Kentaro Furukawa, Kyoko Kanamaru, Masashi Kato, Keietsu Abe, Tetsuo Kobayashi, Takafumi Yamashino, Takeshi Mizuno

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   71 ( 4 )   1003 - 1014   2007年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    Histidine-to-Aspartate (His-Asp) phosphorelay (or two-component) systems are common signal transduction mechanisms implicated in a wide variety of cellular responses to environmental stimuli in both prokaryotes and eukaryotes. For a model filamentous fungi, Aspergillus nidulans, in this study we first compiled a complete list of His-Asp phosphorelay components, including 15 genes for His-kinase (HK), four genes for response regulator. (RR), and only one for histidine-containing phosphotransfer intermediate (HPt). For these RR genes, a set of deletion mutants was constructed so as to create a null allele for each. When examined these mutant strains under various conditions stressful for hyphal growth and asexual spore development, two of them (designated Delta sskA and Delta srrA) showed a marked phenotype of hypersensitivity to oxidative stresses (particularly, to hydrogen peroxide). In this respect, expression of the vegetative-stage specific catB catalase gene was severely impaired in both mutants. Furthermore, conidia from Delta sskA were hypersensitive not only to treatment with H2O2, but also to treatment at aberrantly low (4 degrees C) and high (50 degrees C) temperatures, resulting in reduced germination efficiency. In this respect, not only the catA catalase gene specific for asexual development, but also a set of genes encoding the enzymes for synthesis of certain stress tolerant compatible solutes, such as trehalose and glycerol, were markedly downregulated in conidia from Delta sskA. These results together are indicative of the physiological importance of the His-Asp phosphorelay signaling network involving the SskA and SrrA response regulators.

    DOI: 10.1271/bbb.60665

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  • Characterization of the NikA histidine kinase implicated in the phosphorelay signal transduction of Aspergillus nidulans, with special reference to fungicide responses 査読

    Daisuke Hagiwara, Yoshihiro Matsubayashi, Junichiro Marui, Kentaro Furukawa, Takafumi Yamashino, Kyoko Kanamaru, Masashi Kato, Keietsu Abe, Tetsuo Kobayashi, Takeshi Mizuno

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   71 ( 3 )   844 - 847   2007年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    We recently compiled a complete list of phosphorelay signal transduction components in the model filamentous fungus Aspergillus nidulans. In this study, we characterized a histidine protein kinase (designated NikA) that is found in many fungi, with special reference to responses to potent fungicides (iprodione and fludioxonil). We provided evidence that not only NikA, but also two downstream response regulators (SskA and SrrA) are crucially implicated in the mode of action of these fungicides, and also that the further downstream HogA-MAPK cascade is exaggerated abnormally (or ectopically) in hyphae by the fungicides in a manner dependent on the NikA-SskA phosphorelay.

    DOI: 10.1271/bbb.70051

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  • Aspergillus nidulans HOG pathway is activated only by two-component signalling pathway in response to osmotic stress 査読

    K Furukawa, Y Hoshi, T Maeda, T Nakajima, K Abe

    MOLECULAR MICROBIOLOGY   56 ( 5 )   1246 - 1261   2005年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING LTD  

    Genome sequencing analyses revealed that Aspergillus nidulans has orthologous genes to all those of the high-osmolarity glycerol (HOG) response mitogen-activated protein kinase (MAPK) pathway of Saccharomyces cerevisiae. A. nidulans mutant strains lacking sskA, sskB, pbsB, or hogA, encoding proteins orthologous to the yeast Ssk1p response regulator, Ssk2p/Ssk22p MAPKKKs, Pbs2p MAPKK and Hog1p MAPK, respectively, showed growth inhibition under high osmolarity, and HogA MAPK in these mutants was not phosphorylated under osmotic or oxidative stress. Thus, activation of the A. nidulans HOG (AnHOG) pathway depends solely on the two-component signalling system, and MAPKK activation mechanisms in the AnHOG pathway differ from those in the yeast HOG pathway, where Pbs2p is activated by two branches, Sln1p and Sho1p. Expression of pbsB complemented the high-osmolarity sensitivity of yeast pbs2&UDelta;, and the complementation depended on Ssk2p/Ssk22p, but not on Sho1p. Pbs2p requires its Pro-rich motif for binding to the Src-homology3 (SH3) domain of Sho1p, but PbsB lacks a typical Pro-rich motif. However, a PbsB mutant (PbsB(Pro)) with the yeast Pro-rich motif was activated by the Sho1p branch in yeast. In contrast, HogA in sskA&UDelta; expressing PbsB(Pro) was not phosphorylated under osmotic stress, suggesting that A. nidulans ShoA, orthologous to yeast Sho1p, is not involved in osmoresponsive activation of the AnHOG pathway. We also found that besides HogA, PbsB can activate another Hog1p MAPK orthologue, MpkC, in A. nidulans, although mpkC is dispensable in osmoadaptation. In this study, we discuss the differences between the AnHOG and the yeast HOG pathways.

    DOI: 10.1111/j.1365-2958.2005.04605.x

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  • Disordered cell integrity signaling caused by disruption of the kexB gene in Aspergillus oryzae 査読

    O Mizutani, A Nojima, M Yamamoto, K Furukawa, T Fujioka, Y Yamagata, K Abe, T Nakajima

    EUKARYOTIC CELL   3 ( 4 )   1036 - 1048   2004年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    We isolated the kexB gene, which encodes a subtilisin-like processing enzyme, from a filamentous fungus, Aspergillus oryzae. To examine the physiological role of kexB in A. oryzae, we constructed a kexB disruptant (DeltakexB), which formed shrunken colonies with poor generation of conidia on Czapek-Dox (CD) agar plates and hyperbranched mycelia in CD liquid medium. The phenotypes of the DeltakexB strain were restored under high osmolarity in both solid and liquid culture conditions. We found that transcription of the mpkA gene, which encodes a putative mitogen-activated protein kinase involved in cell integrity signaling, was significantly higher in DeltakexB cells than in wild-type cells. The DeltakexB cells also contained higher levels of transcripts for cell wall-related genes encoding beta-1,3-glucanosyltransferase and chitin synthases, which is presumably attributable to cell integrity signaling through the increased gene expression of mpkA. As expected, constitutively increased levels of phosphorylated MpkA were observed in DeltakexB cells on the CD plate culture. High osmotic stress greatly downregulated the increased levels of both transcripts of mpkA and the phosphorylated form of MpkA in DeltakexB cells, concomitantly suppressing the morphological defects. These results suggest that the upregulation of transcription levels of mpkA and cell wall biogenesis genes in the DeltakexB strain is autoregulated by phosphorylated MpkA as the active form through cell integrity signaling. We think that KexB is required for precise proteolytic processing of sensor proteins in the cell integrity pathway or of cell wall-related enzymes under transcriptional control by the pathway and that the KexB defect thus induces disordered cell integrity signaling.

    DOI: 10.1128/EC.3.4.1036-1048.2004

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  • Isolation and functional analysis of a gene, tcsB, encoding a transmembrane hybrid-type histidine kinase from Aspergillus nidulans 査読

    K Furukawa, Y Katsuno, T Urao, T Yabe, Y Yamada-Okabe, H Yamada-Okabe, Y Yamagata, K Abe, T Nakajima

    APPLIED AND ENVIRONMENTAL MICROBIOLOGY   68 ( 11 )   5304 - 5310   2002年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    We cloned and characterized a novel Aspergillus nidulans histidine kinase gene, tcsB, encoding a membrane-type two-component signaling protein homologous to the yeast osmosensor synthetic lethal N-end rule protein I (SLN1), which transmits signals through the high-osmolarity glycerol response I (HOG1) mitogen-activated protein kinase (MAPK) cascade in yeast cells in response to environmental osmotic stimuli. From an A. nidulans cDNA library, we isolated a positive clone containing a 3,210-bp open reading frame that encoded a putative protein consisting of 1,070 amino acids. The predicted tcsB protein (TcsB) has two probable transmembrane regions in its N-terminal half and has a high degree of structural similarity to yeast Sln1p, a transmembrane hybrid-type histidine kinase. Overexpression of the tcsB cDNA suppressed the lethality of a temperature-sensitive osmosensing-defective sln1-ts yeast mutant. However, tcsB cDNAs in which the conserved phosphorylation site His(552) residue or the phosphorelay site Asp(989) residue had been replaced failed to complement the sln1-ts mutant. In addition, introduction of the tcsB cDNA into an s1n1Delta sho1Delta yeast double mutant, which lacked two osmosensors, suppressed lethality in high-salinity media and activated the HOG1 MAPK. These results imply that TcsB functions as an osmosensor histidine kinase. We constructed an A. nidulans strain lacking the tcsB gene (tcsBDelta) and examined its phenotype. However, unexpectedly, the tcsBDelta strain did not exhibit a detectable phenotype for either hyphal development or morphology on standard or stress media. Our results suggest that A. nidulans has more complex and robust osmoregulatory systems than the yeast SLN1-HOG1 MAPK cascade.

    DOI: 10.1128/AEM.68.11.5304-5310.2002

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MISC

  • リン酸化が制御する出芽酵母のマイトファジー

    古川健太郎, 神吉智丈

    生化学   91 ( 2 )   224 - 227   2019年4月

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  • 酵母におけるマイトファジーの分子機構と生理的役割

    古川健太郎, 神吉智丈

    化学と生物   54 ( 4 )   266 - 272   2016年4月

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  • シグナル伝達経路の人工改変

    古川健太郎

    生物工学会誌   94 ( 1 )   26   2016年1月

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  • 高浸透圧応答の必要条件

    古川健太郎

    生物工学会誌   92 ( 6 )   306   2014年6月

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  • 遺伝子破壊の落とし穴

    古川健太郎

    生物工学会誌   91 ( 5 )   261   2013年5月

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  • 酵母の浸透圧ストレス応答: アクア(グリセロ)ポリンの生理機能と制御機構

    古川健太郎

    化学と生物   50 ( 6 )   398 - 400   2012年6月

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    記述言語:日本語   出版者・発行元:Japan Society for Bioscience, Biotechnology, and Agrochemistry  

    DOI: 10.1271/kagakutoseibutsu.50.398

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    その他リンク: https://jlc.jst.go.jp/DN/JALC/10005923792?from=CiNii

  • 医療に繋がる合成生物学

    古川健太郎

    生物工学会誌   90 ( 5 )   256   2012年5月

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  • 酵母を用いた合成生物学: 新しい人工生命システム構築への挑戦

    古川健太郎

    日本醸造協会誌   106   728 - 736   2011年11月

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  • Aspergillus属の分生子におけるストレス耐性能と制御機構

    萩原大祐, 古川健太郎, 阿部敬悦

    日本醸造協会誌   106   638 - 644   2011年10月

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  • 酵母を用いた合成生物学

    古川健太郎

    生物工学会誌   89 ( 4 )   209   2011年4月

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  • Novel Industrial Applications of Aspergillus oryzae Genomics.

    Keietsu Abe, Kentaro Furukawa, Tomonori Fujioka, Daisuke Hagiwara, Hiroshi Maeda, Junichiro Marui, Osamu Mizutani, Toru Takahashi, Akira Yoshimi, Youhei Yamagata, Katsuya Gomi, Fumihiko Hasegawa

    Aspergillus: Molecular Biology and Genomics   199 - 227   2009年4月

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    記述言語:英語   掲載種別:記事・総説・解説・論説等(その他)   出版者・発行元:Caister Academic Press  

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  • Aspergillus属糸状菌ゲノム情報に基づくMAPKシグナル伝達系の解析

    阿部敬悦, 古川健太郎, 水谷治

    生物の科学 遺伝別冊   21   223 - 227   2007年3月

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受賞

  • 令和4年度新潟大学優秀論文表彰 新潟大学

    2022年11月  

    古川健太郎

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  • 令和3年度新潟大学優秀論文表彰

    2021年12月   新潟大学  

    古川健太郎

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  • 令和2年度新潟大学優秀論文表彰

    2021年1月   新潟大学  

    古川健太郎

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  • 若手奨励賞

    2005年10月   日本農芸化学会 東北支部  

    古川健太郎

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共同研究・競争的資金等の研究

  • マイトファジーの誘導から分解に至る一連の分子機構と生理的意義の解明

    2021年4月 - 2024年3月

    日本学術振興会  基盤研究(C) 

    古川健太郎

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    担当区分:研究代表者 

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  • オートファジーから逃れるタンパク質の網羅的解析

    2020年4月 - 2022年3月

    公益財団法人 発酵研究所  一般研究助成 

    古川 健太郎

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    担当区分:研究代表者 

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  • マイトファジーレセプターAtg32の負の制御機構の解析

    2019年9月 - 2021年8月

    公益財団法人 武田科学振興財団  医学系研究継続助成(基礎) 

    古川健太郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • 酵母におけるミトコンドリアオートファジーの制御機構と生理的意義の統合的理解

    2018年4月 - 2021年3月

    日本学術振興会  基盤研究(C) 

    古川健太郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • ミトコンドリアオートファジーによる分解標的のオミックス解析

    2018年4月 - 2019年3月

    公益財団法人 野田産業科学研究所  奨励研究助成 

    古川健太郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • マイトファジーレセプターAtg32の負の制御機構の解析

    2016年9月 - 2018年8月

    公益財団法人 武田科学振興財団  医学系研究奨励(基礎) 

    古川健太郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • ストレス応答キナーゼを介したマイトファジー制御機構の解明と人工制御

    2016年4月 - 2018年3月

    日本学術振興会  若手研究(B) 

    古川健太郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • ストレス応答キナーゼによるマイトファジー制御機構の解明

    2015年8月 - 2016年3月

    日本学術振興会  研究活動スタート支援 

    古川健太郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • Engineering yeast signalling pathways to understand their design principles

    2013年6月 - 2014年12月

    Stiftelsen Olle Engkvist Byggmästare  Research grant 

    古川健太郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • Synthetic biology: Engineering signal transduction pathways towards an implementation of novel biotechnological systems

    2012年4月 - 2013年5月

    Stiftelsen Olle Engkvist Byggmästare  Research grant 

    古川健太郎

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    担当区分:研究代表者  資金種別:競争的資金

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  • アスペルギス属カビの高浸透圧応答シグナル伝達系に関する研究

    2004年4月 - 2006年3月

    日本学術振興会  特別研究員奨励費 

    古川健太郎

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    担当区分:研究代表者  資金種別:競争的資金

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担当経験のある授業科目(researchmap)

  • 医学研究実習

    機関名:新潟大学医学部医学科

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  • ジャーナルクラブ

    機関名:新潟大学医学部医学科

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社会貢献活動

  • 令和元年度先端科学技術活用講座 (高等学校)

    役割:講師

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