2022/05/26 更新

写真a

スギエ アツシ
杉江 淳
SUGIE Atsushi
所属
脳研究所 生命科学リソース研究センター 准教授
職名
准教授
外部リンク

学位

  • 博士(理学) ( 2010年9月   東京大学 )

経歴(researchmap)

  • 新潟大学   脳研究所   准教授

    2020年4月 - 現在

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  • 新潟大学   超域学術院   助教

    2016年2月 - 2020年3月

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  • ドイツ神経変性疾患研究所   Tavosanis研究室

    2011年12月 - 2016年2月

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  • ドイツ マックスプランク研究所 神経生物学   鈴木研究室

    2010年10月 - 2011年12月

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  • 株式会社DHC   研究開発部 分析化学研究室   主任

    2005年4月 - 2007年3月

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経歴

  • 新潟大学   研究推進機構 超域学術院   准教授

    2020年4月 - 現在

  • 新潟大学   研究推進機構 超域学術院   助教

    2016年2月 - 2020年3月

学歴

  • 東京大学大学院   理学系研究科   生物化学専攻

    2007年4月 - 2010年9月

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  • 神戸大学大学院   自然科学研究科   生物環境制御学科

    2003年4月 - 2005年3月

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  • 神戸大学   農学部   生物環境制御学科

    1999年4月 - 2003年3月

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所属学協会

 

論文

  • A quantitative model of sporadic axonal degeneration in the Drosophila visual system. 国際誌

    Mélisande Richard, Karolína Doubková, Yohei Nitta, Hiroki Kawai, Atsushi Sugie, Gaia Tavosanis

    The Journal of neuroscience : the official journal of the Society for Neuroscience   2022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)  

    In human neurodegenerative diseases, neurons undergo axonal degeneration months to years before they die. Here, we developed a system modelling early degenerative events in Drosophila adult photoreceptor cells. Thanks to the stereotypy of their axonal projections, this system delivers quantitative data on sporadic and progressive axonal degeneration of photoreceptor cells. Using this method, we show that exposure of adult female flies to a constant light stimulation for several days overcomes the intrinsic resilience of R7 photoreceptors and leads to progressive axonal degeneration. This was not associated with apoptosis. We furthermore provide evidence that loss of synaptic integrity between R7 and a postsynaptic partner preceded axonal degeneration, thus recapitulating features of human neurodegenerative diseases. Finally, our experiments uncovered a role of postsynaptic partners of R7 to initiate degeneration, suggesting that postsynaptic cells signal back to the photoreceptor to maintain axonal structure. This model can be used to dissect cellular and circuit mechanisms involved in the early events of axonal degeneration, allowing for a better understanding of how neurons cope with stress and lose their resilience capacities.SIGNIFICANCE STATEMENT:Neurons can be active and functional for several years. In the course of ageing and in disease conditions leading to neurodegeneration, subsets of neurons lose their resilience and start dying. What initiates this turning point at the cellular level is not clear. Here, we developed a model allowing to systematically describe this phase. The loss of synapses and axons represents an early and functionally relevant event towards degeneration. Utilizing the ordered distribution of Drosophila photoreceptors axon terminals, we assembled a system to study sporadic initiation of axon loss and delineated a role for non-cell-autonomous activity regulation in the initiation of axon degeneration. This work will help shedding light on key steps in the etiology of non-familial cases of neurodegenerative diseases.

    DOI: 10.1523/JNEUROSCI.2115-21.2022

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  • Detoxification of amyloid β fibrils by curcumin derivatives and their verification in a Drosophila Alzheimer's model. 国際誌

    Rohmad Yudi Utomo, Atsushi Sugie, Satoshi Okada, Kazuki Miura, Hiroyuki Nakamura

    Chemical communications (Cambridge, England)   58 ( 15 )   2576 - 2579   2022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)  

    Curcumin derivatives B and N were developed as disaggregation agents of amyloid β (Aβ) fibrils. The detoxification provided by each compound at a concentration of 1 μM was observed in neuroblastoma cells. Furthermore, both compounds significantly rescued locomotion dysfunction in an Aβ-expressing Drosophila model of Alzheimer's disease.

    DOI: 10.1039/d1cc07000b

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  • Candesartan prevents arteriopathy progression in cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy model. 国際誌

    Taisuke Kato, Ri-Ichiroh Manabe, Hironaka Igarashi, Fuyuki Kametani, Sachiko Hirokawa, Yumi Sekine, Natsumi Fujita, Satoshi Saito, Yusuke Kawashima, Yuya Hatano, Shoichiro Ando, Hiroaki Nozaki, Akihiro Sugai, Masahiro Uemura, Masaki Fukunaga, Toshiya Sato, Akihide Koyama, Rie Saito, Atsushi Sugie, Yasuko Toyoshima, Hirotoshi Kawata, Shigeo Murayama, Masaki Matsumoto, Akiyoshi Kakita, Masato Hasegawa, Masafumi Ihara, Masato Kanazawa, Masatoyo Nishizawa, Shoji Tsuji, Osamu Onodera

    The Journal of clinical investigation   131 ( 22 )   2021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)  

    Cerebral small vessel disease (CSVD) causes dementia and gait disturbance due to arteriopathy. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a hereditary form of CSVD caused by loss of high-temperature requirement A1 (HTRA1) serine protease activity. In CARASIL, arteriopathy causes intimal thickening, smooth muscle cell (SMC) degeneration, elastic lamina splitting, and vasodilation. The molecular mechanisms were proposed to involve the accumulation of matrisome proteins as substrates or abnormalities in transforming growth factor β (TGF-β) signaling. Here, we show that HTRA1-/- mice exhibited features of CARASIL-associated arteriopathy: intimal thickening, abnormal elastic lamina, and vasodilation. In addition, the mice exhibited reduced distensibility of the cerebral arteries and blood flow in the cerebral cortex. In the thickened intima, matrisome proteins, including the hub protein fibronectin (FN) and latent TGF-β binding protein 4 (LTBP-4), which are substrates of HTRA1, accumulated. Candesartan treatment alleviated matrisome protein accumulation and normalized the vascular distensibility and cerebral blood flow. Furthermore, candesartan reduced the mRNA expression of Fn1, Ltbp-4, and Adamtsl2, which are involved in forming the extracellular matrix network. Our results indicate that these accumulated matrisome proteins may be potential therapeutic targets for arteriopathy in CARASIL.

    DOI: 10.1172/JCI140555

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  • De novo ARF3 variants cause neurodevelopmental disorder with brain abnormality. 査読 国際誌

    Masamune Sakamoto, Kazunori Sasaki, Atsushi Sugie, Yohei Nitta, Tetsuaki Kimura, Semra Gürsoy, Tayfun Cinleti, Mizue Iai, Toru Sengoku, Kazuhiro Ogata, Atsushi Suzuki, Nobuhiko Okamoto, Kazuhiro Iwama, Naomi Tsuchida, Yuri Uchiyama, Eriko Koshimizu, Atsushi Fujita, Kohei Hamanaka, Satoko Miyatake, Takeshi Mizuguchi, Masataka Taguri, Shuuichi Ito, Hidehisa Takahashi, Noriko Miyake, Naomichi Matsumoto

    Human molecular genetics   2021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)  

    An optimal Golgi transport system is important for mammalian cells. The adenosine diphosphate (ADP) ribosylation factors (ARF) are key proteins for regulating cargo sorting at the Golgi network. In this family, ARF3 mainly works at the trans-Golgi network (TGN), and no ARF3-related phenotypes have yet been described in humans. We here report the clinical and genetic evaluations of two unrelated children with de novo pathogenic variants in the ARF3 gene: c.200A > T (p.Asp67Val) and c.296G > T (p.Arg99Leu). Although the affected individuals presented commonly with developmental delay, epilepsy, and brain abnormalities, there were differences in severity, clinical course, and brain lesions. In vitro subcellular localization assays revealed that the p.Arg99Leu mutant localized to Golgi apparatus, similar to the wild-type, whereas the p.Asp67Val mutant tended to show a disperse cytosolic pattern together with abnormally dispersed Golgi localization, similar to that observed in a known dominant negative variant (p.Thr31Asn). Pull-down assays revealed that the p.Asp67Val had a loss-of-function effect and the p.Arg99Leu variant had increased binding of the adaptor protein, Golgi-localized, γ-adaptin ear-containing, ARF-binding protein 1 (GGA1), supporting the gain of function. Furthermore, in vivo studies revealed that p.Asp67Val transfection led to lethality in flies. In contrast, flies expressing p.Arg99Leu had abnormal rough eye, as observed in the gain-of-function variant p.Gln71Leu. These data indicate that two ARF3 variants, the possibly loss-of-function p.Asp67Val and the gain-of-function p.Arg99Leu, both impair the Golgi transport system. Therefore, it may not be unreasonable that they showed different clinical features like diffuse brain atrophy (p.Asp67Val) and cerebellar hypoplasia (p.Arg99Leu).

    DOI: 10.1093/hmg/ddab224

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  • Glial insulin regulates cooperative or antagonistic Golden goal/Flamingo interactions during photoreceptor axon guidance. 査読 国際誌

    Hiroki Takechi, Satoko Hakeda-Suzuki, Yohei Nitta, Yuichi Ishiwata, Riku Iwanaga, Makoto Sato, Atsushi Sugie, Takashi Suzuki

    eLife   10   2021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)  

    Transmembrane protein Golden goal (Gogo) interacts with atypical cadherin Flamingo (Fmi) to direct R8 photoreceptor axons in the Drosophila visual system. However, the precise mechanisms underlying Gogo regulation during columnar- and layer-specific R8 axon targeting are unknown. Our studies demonstrated that the insulin secreted from surface and cortex glia switches the phosphorylation status of Gogo, thereby regulating its two distinct functions. Non-phosphorylated Gogo mediates the initial recognition of the glial protrusion in the center of the medulla column, whereas phosphorylated Gogo suppresses radial filopodia extension by counteracting Flamingo to maintain a one axon-to-one column ratio. Later, Gogo expression ceases during the midpupal stage, thus allowing R8 filopodia to extend vertically into the M3 layer. These results demonstrate that the long- and short-range signaling between the glia and R8 axon growth cones regulates growth cone dynamics in a stepwise manner, and thus shapes the entire organization of the visual system.

    DOI: 10.7554/eLife.66718

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  • Analysing the evolutional and functional differentiation of four types of Daphnia magna cryptochrome in Drosophila circadian clock. 査読 国際誌

    Yohei Nitta, Sayaka Matsui, Yukine Kato, Yosuke Kaga, Kenkichi Sugimoto, Atsushi Sugie

    Scientific reports   9 ( 1 )   8857 - 8857   2019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)  

    Cryptochrome (CRY) plays an important role in the input of circadian clocks in various species, but gene copies in each species are evolutionarily divergent. Type I CRYs function as a photoreceptor molecule in the central clock, whereas type II CRYs directly regulate the transcriptional activity of clock proteins. Functions of other types of animal CRYs in the molecular clock remain unknown. The water flea Daphnia magna contains four Cry genes. However, it is still difficult to analyse these four genes. In this study, we took advantage of powerful genetic resources available from Drosophila to investigate evolutionary and functional differentiation of CRY proteins between the two species. We report differences in subcellular localisation of each D. magna CRY protein when expressed in the Drosophila clock neuron. Circadian rhythm behavioural experiments revealed that D. magna CRYs are not functionally conserved in the Drosophila molecular clock. These findings provide a new perspective on the evolutionary conservation of CRY, as functions of the four D. magna CRY proteins have diverse subcellular localisation levels. Furthermore, molecular clocks of D. magna have been evolutionarily differentiated from those of Drosophila. This study highlights the extensive functional diversity existing among species in their complement of Cry genes.

    DOI: 10.1038/s41598-019-45410-w

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  • Structural aspects of plasticity in the nervous system of Drosophila. 査読

    Sugie A, Marchetti G, Tavosanis G

    Neural development   13 ( 1 )   14   2018年7月

  • Identification of glaikit in a genome-wide expression profiling for axonal bifurcation of the mushroom body in Drosophila 査読

    Yohei Nitta, Atsushi Sugie

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   487 ( 4 )   898 - 902   2017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:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Axonal branching is a fundamental requirement for sending electrical signals to multiple targets. However, despite the importance of axonal branching in neural development and function, the molecular mechanisms that control branch formation are poorly understood. Previous studies have hardly addressed the intracellular signaling cascade of axonal bifurcation characterized by growth cone splitting. Recently we reported that DISCO interacting protein 2 (DIP2) regulates bifurcation of mushroom body axons in Drosophila melanogaster. DIP2 mutant displays ectopic bifurcations in alpha/beta neurons. Taking advantage of this phenomenon, we tried to identify genes involved in branching formation by comparing the transcriptome of wild type with that of DIP2 RNAi flies. After the microarray analysis, Glaikit (Gkt), a member of the phospholipase D superfamily, was identified as a downstream target of DIP2 by RNAi against gkt and qRT-PCR experiment. Single cell MARCM analysis of gkt mutant phenocopied the ectopic axonal branches observed in DIP2 mutant. Furthermore, a genetic analysis between gkt and DIP2 revealed that gkt potentially acts in parallel with DIP2. In conclusion, we identified a novel gene underlying the axonal bifurcation process. (C) 2017 The Authors. Published by Elsevier Inc.

    DOI: 10.1016/j.bbrc.2017.04.150

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  • DISCO interacting protein 2 determines direction of axon projection under the regulation of c-Jun N-terminal kinase in the Drosophila mushroom body 査読

    Yohei Nitta, Atsushi Sugie

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   487 ( 1 )   116 - 121   2017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)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Precisely controlled axon guidance for complex neuronal wiring is essential for appropriate neuronal function. c-Jun N-terminal kinase (INK) was found to play a role in axon guidance recently as well as in cell proliferation, protection and apoptosis. In spite of many genetic and molecular studies on these biological processes regulated by JNK, how JNK regulates axon guidance accurately has not been fully explained thus far. To address this question, we use the Drosophila mushroom body (MB) as a model since the alpha/beta axons project in two distinct directions. Here we show that DISCO interacting protein 2 (DIP2) is required for the accurate direction of axonal guidance. DIP2 expression is under the regulation of Basket (Bsk), the Drosophila homologue of JNK. We additionally found that the Bsk/DIP2 pathway is independent from the AP-I transcriptional factor complex pathway, which is directly activated by Bsk. In conclusion, our findings revealed DIP2 as a novel effector downstream of Bsk modulating the direction of axon projection. (C) 2017 The Authors. Published by Elsevier Inc.

    DOI: 10.1016/j.bbrc.2017.04.028

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  • Analyzing Synaptic Modulation of Drosophila melanogaster Photoreceptors after Exposure to Prolonged Light 査読

    Atsushi Sugie, Christoph Moehl, Satoko Hakeda-Suzuki, Hideaki Matsui, Takashi Suzuki, Gaia Tavosanis

    JOVE-JOURNAL OF VISUALIZED EXPERIMENTS   ( 120 )   2017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)   出版者・発行元:JOURNAL OF VISUALIZED EXPERIMENTS  

    The nervous system has the remarkable ability to adapt and respond to various stimuli. This neural adjustment is largely achieved through plasticity at the synaptic level. The Active Zone (AZ) is the region at the presynaptic membrane that mediates neurotransmitter release and is composed of a dense collection of scaffold proteins. AZs of Drosophila melanogaster (Drosophila) photoreceptors undergo molecular remodeling after prolonged exposure to natural ambient light. Thus the level of neuronal activity can rearrange the molecular composition of the AZ and contribute to the regulation of the functional output.
    Starting from the light exposure set-up preparation to the immunohistochemistry, this protocol details how to quantify the number, the spatial distribution, and the delocalization level of synaptic molecules at AZs in Drosophila photoreceptors. Using image analysis software, clusters of the GFP-fused AZ component Bruchpilot were identified for each R8 photoreceptor (R8) axon terminal. Detected Bruchpilot spots were automatically assigned to individual R8 axons. To calculate the distribution of spot frequency along the axon, we implemented a customized software plugin. Each axon's start-point and end-point were manually defined and the position of each Bruchpilot spot was projected onto the connecting line between start and end-point. Besides the number of Bruchpilot clusters, we also quantified the delocalization level of BruchpilotGFP within the clusters. These measurements reflect in detail the spatially resolved synaptic dynamics in a single neuron under different environmental conditions to stimuli.

    DOI: 10.3791/55176

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  • DISCO Interacting Protein 2 regulates axonal bifurcation and guidance of Drosophila mushroom body neurons 査読

    Yohei Nitta, Daisuke Yamazaki, Atsushi Sugie, Makoto Hiroi, Tetsuya Tabata

    DEVELOPMENTAL BIOLOGY   421 ( 2 )   233 - 244   2017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:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Axonal branching is one of the key processes within the enormous complexity of the nervous system to enable a single neuron to send information to multiple targets. However, the molecular mechanisms that control branch formation are poorly understood. In particular, previous studies have rarely addressed the mechanisms underlying axonal bifurcation, in which axons form new branches via splitting of the growth cone. We demonstrate that DISCO Interacting Protein 2 (DIP2) is required for precise axonal bifurcation in Drosophila mushroom body (MB) neurons by suppressing ectopic bifurcation and regulating the guidance of sister axons. We also found that DIP2 localize to the plasma membrane. Domain function analysis revealed that the AMP-synthetase domains of DIP2 are essential for its function, which may involve exerting a catalytic activity that modifies fatty acids. Genetic analysis and subsequent biochemical analysis suggested that DIP2 is involved in the fatty acid metabolization of acyl-CoA. Taken together, our results reveal a function of DIP2 in the developing nervous system and provide a potential functional relationship between fatty acid metabolism and axon morphogenesis.

    DOI: 10.1016/j.ydbio.2016.11.015

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  • Molecular Remodeling of the Presynaptic Active Zone of Drosophila Photoreceptors via Activity-Dependent Feedback 査読

    Atsushi Sugie, Satoko Hakeda-Suzuki, Emiko Suzuki, Marion Silies, Mai Shimozono, Christoph Moehl, Takashi Suzuki, Gaia Tavosanis

    NEURON   86 ( 3 )   711 - 725   2015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)   出版者・発行元:CELL PRESS  

    Neural activity contributes to the regulation of the properties of synapses in sensory systems, allowing for adjustment to a changing environment. Little is known about how synaptic molecular components are regulated to achieve activity-dependent plasticity at central synapses. Here, we found that after prolonged exposure to natural ambient light the presynaptic active zone in Drosophila photoreceptors undergoes reversible remodeling, including loss of Bruchpilot, DLiprin-alpha, and DRBP, but not of DSyd-1 or Cacophony. The level of depolarization of the postsynaptic neurons is critical for the light-induced changes in active zone composition in the photoreceptors, indicating the existence of a feedback signal. In search of this signal, we have identified a crucial role of microtubule meshwork organization downstream of the divergent canonical Wnt pathway, potentially via Kinesin-3 Imac. These data reveal that active zone composition can be regulated in vivo and identify the underlying molecular machinery.

    DOI: 10.1016/j.neuron.2015.03.046

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  • Assessing the Role of Cell-Surface Molecules in Central Synaptogenesis in the Drosophila Visual System 査読

    Sandra Berger-Mueller, Atsushi Sugie, Fumio Takahashi, Gaia Tavosanis, Satoko Hakeda-Suzuki, Takashi Suzuki

    PLOS ONE   8 ( 12 )   e83732   2013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:PUBLIC LIBRARY SCIENCE  

    A hallmark of the central nervous system is its spatial and functional organization in synaptic layers. During neuronal development, axons form transient contacts with potential post-synaptic elements and establish synapses with appropriate partners at specific layers. These processes are regulated by synaptic cell-adhesion molecules. In the Drosophila visual system, R7 and R8 photoreceptor subtypes target distinct layers and form en passant pre-synaptic terminals at stereotypic loci of the axonal shaft. A leucine-rich repeat transmembrane protein, Capricious (Caps), is known to be selectively expressed in R8 axons and their recipient layer, which led to the attractive hypothesis that Caps mediates R8 synaptic specificity by homophilic adhesion. Contradicting this assumption, our results indicate that Caps does not have a prominent role in synaptic-layer targeting and synapse formation in Drosophila photoreceptors, and that the specific recognition of the R8 target layer does not involve Caps homophilic axon-target interactions. We generated flies that express a tagged synaptic marker to evaluate the presence and localization of synapses in R7 and R8 photoreceptors. These genetic tools were used to assess how the synaptic profile is affected when axons are forced to target abnormal layers by expressing axon guidance molecules. When R7 axons were mistargeted to the R8-recipient layer, R7s either maintained an R7-like synaptic profile or acquired a similar profile to r8s depending on the overexpressed protein. When R7 axons were redirected to a more superficial medulla layer, the number of presynaptic terminals was reduced. These results indicate that cell-surface molecules are able to dictate synapse loci by changing the axon terminal identity in a partially cell-autonomous manner, but that presynapse formation at specific sites also requires complex interactions between pre- and post-synaptic elements.

    DOI: 10.1371/journal.pone.0083732

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  • Recognition of pre- and postsynaptic neurons via nephrin/NEPH1 homologs is a basis for the formation of the Drosophila retinotopic map 査読

    Atsushi Sugie, Daiki Umetsu, Tetsuo Yasugi, Karl-Friedrich Fischbach, Tetsuya Tabata

    DEVELOPMENT   137 ( 19 )   3303 - 3313   2010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:COMPANY OF BIOLOGISTS LTD  

    Topographic maps, which maintain the spatial order of neurons in the order of their axonal connections, are found in many parts of the nervous system. Here, we focus on the communication between retinal axons and their postsynaptic partners, lamina neurons, in the first ganglion of the Drosophila visual system, as a model for the formation of topographic maps. Post-mitotic lamina precursor cells differentiate upon receiving Hedgehog signals delivered through newly arriving retinal axons and, before maturing to extend neurites, extend short processes toward retinal axons to create the lamina column. The lamina column provides the cellular basis for establishing stereotypic synapses between retinal axons and lamina neurons. In this study, we identified two cell-adhesion molecules: Hibris, which is expressed in post-mitotic lamina precursor cells; and Roughest, which is expressed on retinal axons. Both proteins belong to the nephrin/NEPH1 family. We provide evidence that recognition between post-mitotic lamina precursor cells and retinal axons is mediated by interactions between Hibris and Roughest. These findings revealed mechanisms by which axons of presynaptic neurons deliver signals to induce the development of postsynaptic partners at the target area. Postsynaptic partners then recognize the presynaptic axons to make ensembles, thus establishing a topographic map along the anterior/posterior axis.

    DOI: 10.1242/dev.047332

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  • Coordinated sequential action of EGFR and Notch signaling pathways regulates proneural wave progression in the Drosophila optic lobe 査読

    Tetsuo Yasugi, Atsushi Sugie, Daiki Umetsu, Tetsuya Tabata

    DEVELOPMENT   137 ( 19 )   3193 - 3203   2010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:COMPANY OF BIOLOGISTS LTD  

    During neurogenesis in the medulla of the Drosophila optic lobe, neuroepithelial cells are programmed to differentiate into neuroblasts at the medial edge of the developing optic lobe. The wave of differentiation progresses synchronously in a row of cells from medial to the lateral regions of the optic lobe, sweeping across the entire neuroepithelial sheet; it is preceded by the transient expression of the proneural gene lethal of scute [l(1)sc] and is thus called the proneural wave. We found that the epidermal growth factor receptor (EGFR) signaling pathway promotes proneural wave progression. EGFR signaling is activated in neuroepithelial cells and induces l(1) sc expression. EGFR activation is regulated by transient expression of Rhomboid (Rho), which is required for the maturation of the EGF ligand Spitz. Rho expression is also regulated by the EGFR signal. The transient and spatially restricted expression of Rho generates sequential activation of EGFR signaling and assures the directional progression of the differentiation wave. This study also provides new insights into the role of Notch signaling. Expression of the Notch ligand Delta is induced by EGFR, and Notch signaling prolongs the proneural state. Notch signaling activity is downregulated by its own feedback mechanism that permits cells at proneural states to subsequently develop into neuroblasts. Thus, coordinated sequential action of the EGFR and Notch signaling pathways causes the proneural wave to progress and induce neuroblast formation in a precisely ordered manner.

    DOI: 10.1242/dev.048058

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  • Sunspot, a link between Wingless signaling and endoreplication in Drosophila 査読

    Kenzui Taniue, Ayumu Nishida, Fumihiko Hamada, Atsushi Sugie, Takeaki Oda, Kumiko Ui-Tei, Tetsuya Tabata, Tetsu Akiyama

    DEVELOPMENT   137 ( 10 )   1755 - 1764   2010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)   出版者・発行元:COMPANY OF BIOLOGISTS LTD  

    The Wingless (Wg)/Wnt signaling pathway is highly conserved throughout many multicellular organisms. It directs the development of diverse tissues and organs by regulating important processes such as proliferation, polarity and the specification of cell fates. Upon activation of the Wg/Wnt signaling pathway, Armadillo (Arm)/beta-catenin is stabilized and interacts with the TCF family of transcription factors, which in turn activate Wnt target genes. We show here that Arm interacts with a novel BED (BEAF and Dref) finger protein that we have termed Sunspot (Ssp). Ssp transactivates Drosophila E2F-1 (dE2F-1) and PCNA expression, and positively regulates the proliferation of imaginal disc cells and the endoreplication of salivary gland cells. Wg negatively regulates the function of Ssp by changing its subcellular localization in the salivary gland. In addition, Ssp was found not to be involved in the signaling pathway mediated by Arm associated with dTCF. Our findings indicate that Arm controls development in part by regulating the function of Ssp.

    DOI: 10.1242/dev.042077

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  • Mitochondrial alternative pathway is associated with development of freezing tolerance in common wheat 査読

    Nobuyuki Mizuno, Atsushi Sugie, Fuminori Kobayashi, Shigeo Takumi

    JOURNAL OF PLANT PHYSIOLOGY   165 ( 4 )   462 - 467   2008年

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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 GMBH, URBAN & FISCHER VERLAG  

    Cold acclimation is an adaptive process for acquiring cold/freezing tolerance in wheat. To clarify the cultivar difference of freezing tolerance, we compared mitochondrial respiration activity and the expression profile of alternative oxidase (AOX) genes under low-temperature conditions using two common wheat cultivars differing in freezing tolerance. During cold acclimation, the respiration capacity of the alternative pathway significantly increased in a freezing-tolerant cultivar compared with a freezing-sensitive cultivar. More abundant accumulation of the AOX and uncoupling protein gene transcripts was also observed under the low-temperature conditions in the tolerant cultivar than in the sensitive cultivar. These results suggest that the mitochondrial alternative pathway might be partly associated with the cold acclimation and freezing tolerance in wheat. (C) 2007 Elsevier GmbH. All rights reserved.

    DOI: 10.1016/j.jplph.2007.04.004

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  • Alteration of respiration capacity and transcript accumulation level of alternative oxidase genes in necrosis lines of common wheat 査読

    Atsushi Sugie, Koji Murai, Shigeo Takumi

    GENES & GENETIC SYSTEMS   82 ( 3 )   231 - 239   2007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:GENETICS SOC JAPAN  

    Mitochondrial alternative oxidase (AOX) is the terminal oxidase responsible for cyanide-insensitive and salicylhydroxamic acid-sensitive respiration in plants. AOX is a key enzyme of the alternative respiration pathway. To study the effects of necrotic cell death on the mitochondrial function, production of reactive oxygen species (ROS), respiration capacities and accumulation patterns of mitochondria-targeted protein-encoding gene transcripts were compared between wild-type, lesion-mimic mutant and hybrid necrosis wheat plants. Around cells with the necrosis symptom, ROS accumulated abundantly in the intercellular spaces. The ratio of the alternative pathway to the cytochrome pathway was markedly enhanced in the necrotic leaves. Transcripts of a wheat AOX gene, Waox1a, were more abundant in a novel lesion-mimic mutant of common wheat than in the wildtype plants. An increased level of the Waox1a transcripts was also observed in hybrid plants containing Ne1 and Ne2 genes. These results indicated that an increase of the wheat AOX transcript level resulted in enhancement of respiration capacity of the alternative pathway in the necrotic cells.

    DOI: 10.1266/ggs.82.231

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  • Overexpression of wheat alternative oxidase gene Waox1a alters respiration capacity and response to reactive oxygen species under low temperature in transgenic Arabidopsis 査読

    Atsushi Sugie, Nayden Naydenov, Nobuyuki Mizuno, Chiharu Nakamura, Shigeo Takumi

    GENES & GENETIC SYSTEMS   81 ( 5 )   349 - 354   2006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:GENETICS SOC JAPAN  

    Under low temperature conditions, the cytochrome pathway of respiration is repressed and reactive oxygen species (ROS) are produced in plants. Mitochondrial alternative oxidase (AOX) is the terminal oxidase responsible for the cyanide-insensitive and salicylhydroxamic acid-sensitive respiration. To study functions of wheat AOX genes under low temperature, we produced transgenic Arabidopsis by introducing Waox1a expressed under control of the cauliflower mosaic virus (CaMV) 35S promoter in Arabidopsis thaliana. The enhancement of endogenous AOX1a expression via low temperature stress was delayed in the transgenic Arabidopsis. Recovery of the total respiration activity under low temperature occurred more rapidly in the transgenic plants than in the wild-type plants due to a constitutively increased alternative pathway capacity. Levels of ROS decreased in the transgenic plants under low temperature stress. These results support the hypothesis that AOX alleviates oxidative stress when the cytochrome pathway of respiration is inhibited under abiotic stress conditions.

    DOI: 10.1266/ggs.81.349

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MISC

  • 後シナプスニューロンの神経活動に依存的なフィードバックシグナルを介したショウジョウバエの視細胞における活性帯の構成タンパク質の再編成 招待

    杉江 淳, Tavosanis Gaia, 鈴木 崇之

    ライフサイエンス新着論文レビュー   2015年

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)  

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  • Molecular remodeling of the presynaptic active zone of Drosophila photoreceptors via an activity-dependent feedback signal

    Atsushi Sugie, Satoko Hakeda, Emiko Suzuki, Gaia Tavosanis, Takashi Suzuki

    GENES & GENETIC SYSTEMS   89 ( 6 )   318 - 318   2014年12月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:GENETICS SOC JAPAN  

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  • A Genetic approach to elucidate the central synapse plasticity

    Atsushi Sugie, Satoko Hakeda, Emiko Suzuki, Gaia Tavosanis, Takashi Suzuki

    GENES & GENETIC SYSTEMS   88 ( 6 )   339 - 339   2013年12月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:GENETICS SOC JAPAN  

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  • 神経回路形成におけるシナプス前後細胞間認識に必要な因子の網羅的探索:ショウジョウバエ視覚系神経節の形成をモデルとして

    杉江淳, 梅津大輝, 多羽田哲也

    生化学   2008年

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  • Structural diversity of the wheat nuclear gene waox1a encoding mitochondrial alternative oxidase, a single unique enzyme in the cyanide-resistant alternative pathway 査読

    N. Naydenov, S. Takumi, A. Sugie, Y. Ogihara, A. Atanassov, C. Nakamura

    Biotechnology and Biotechnological Equipment   19 ( 1 )   48 - 56   2005年

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    記述言語:英語  

    Alternative respiratory pathways other than the main cytochrome pathway are present in plant mitochondria, one of which is represented by a single unique enzyme alternative oxidase (AOX). Two genes encoding AOX proteins in common wheat have already been characterized (24). To further understand the structural diversity of the Aox genes in wheat, we screened the common wheat genome library for additional members of this small multigene family. Twelve Aox-related sequences were detected by Southern blot and restriction analyses and four of them were successfully subcloned and sequenced. All of the newly isolated sequences appear to be more closely related to the wheat gene Waox1a than Waox1c. Structural analysis showed that one clone was identical to Waox1a and three others appeared to be non-functional as they contained insertion/deletion mutations and/or frame-shift mutations leading to in-frame stop codons on different locations. In addition, one genomic clone highly homologous to the Waox1a cDNA sequence was identified. This cDNA-like sequence was also identified in the genomes of diploid, tetraploid and hexaploid wheat accessions. Although its origin remained unknown, our result indicated that it evolved before divergence of the ancestral wheat genomes. © 2005 Taylor and Francis Group, LLC.

    DOI: 10.1080/13102818.2005.10817153

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講演・口頭発表等

  • ショウジョウバエを用いた軸索変性の初期病態解析

    第14回日本ショウジョウバエ研究集会  2021年9月 

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    開催年月日: 2021年9月

    記述言語:英語   会議種別:口頭発表(一般)  

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  • ショウジョウバエをモデルとした細胞間コミュニケーション障害を伴う神経変性過程の解析

    第43回日本神経科学大会  2020年7月 

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    記述言語:英語   会議種別:口頭発表(一般)  

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  • Elucidation of neurodegenerative process with mitochondrial dysfunction using Drosophila model 招待

    杉江 淳

    The 92nd annual meeting of the Japanese biochemical society  2019年9月 

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    記述言語:英語   会議種別:シンポジウム・ワークショップ パネル(公募)  

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  • Elucidation of neurodegenerative process with impairment of intercellular communication using Drosophila model 招待

    杉江 淳

    NEURO2019  2019年7月 

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    記述言語:英語   会議種別:シンポジウム・ワークショップ パネル(公募)  

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  • Synaptic and neuronal degeneration through the excessive visual stimulation.

    杉江 淳

    The 41rd Annual Meeting of the Japan Neuroscience Society  2018年7月 

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    記述言語:英語   会議種別:口頭発表(一般)  

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共同研究・競争的資金等の研究

  • タウオパチー病態機序解明を目指すゲノムリソースの網羅的機能解析

    研究課題/領域番号:21H02837  2021年4月 - 2024年3月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    杉江 淳, 池内 健, 新田 陽平

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    配分額:17680000円 ( 直接経費:13600000円 、 間接経費:4080000円 )

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  • シヌクレイノパチーにおける病態伝播マスター遺伝子の網羅的探索

    2019年7月 - 2021年3月

    日本学術振興会  挑戦的研究(萌芽) 

    杉江 淳, 永井 義隆, 鈴木 マリ

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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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  • 人工光が引き起こすトリパータイトシナプス障害の発症機序解明

    2018年9月 - 2020年3月

    武田科学振興財団  ライフサイエンス研究助成 

    杉江 淳

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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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  • 知覚細胞の変性メカニズムの解明

    2018年8月 - 2019年3月

    永井NS知覚科学振興財団  助成金 

    杉江 淳

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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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  • TDP-43の細胞外放出機構と細胞内取り込み機構の解明

    2017年6月 - 2018年3月

    成茂神経科学研究助成基金  助成金 

    杉江 淳

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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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  • 前シナプスの神経細胞保護機能における活性体構造変化の重要性の検討

    2017年4月 - 2020年3月

    日本学術振興会  若手研究(A) 

    杉江 淳

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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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  • TDP-43が細胞間を伝播するメカニズムの解明

    2017年4月 - 2018年3月

    公益信託「生命の彩」  ALSの研究助成基金 

    杉江 淳

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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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  • トランスクリプトーム解析による神経変性疾患間の比較

    2017年2月 - 2019年3月

    上原記念生命科学財団  研究奨励金 

    杉江 淳

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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

  • 先端医科学研究概説

    2022年
    -
    現在
    機関名:新潟大学

  • 遺伝看護学特論Ⅱ

    2020年
    -
    現在
    機関名:新潟大学

  • 遺伝看護学特論Ⅵ

    2020年
    -
    現在
    機関名:新潟大学

  • 遺伝看護学特論Ⅰ

    2020年
    -
    現在
    機関名:新潟大学