2024/11/10 更新

写真a

マツイ ノリコ
松井 典子
MATSUI Noriko
所属
脳研究所 生命科学リソース研究センター 特任助手
職名
特任助手
外部リンク

経歴

  • 新潟大学   脳研究所 生命科学リソース研究センター   特任助手

    2021年4月 - 現在

 

論文

  • GPATCH4 contributes to nucleolus morphology and its dysfunction impairs cell viability. 国際誌

    Kazuki Kodera, Ryuichi Hishida, Akiko Sakai, Hiromi Nyuzuki, Noriko Matsui, Tomoyuki Yamanaka, Akihiko Saitoh, Hideaki Matsui

    Biochemical and biophysical research communications   693   149384 - 149384   2023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)  

    The nucleolus serves a multifaceted role encompassing not only rRNA transcription and ribosome synthesis, but also the intricate orchestration of cell cycle regulation and the modulation of cellular senescence. G-patch domain containing 4 (GPATCH4) stands as one among the nucleolar proteins; however, its functional significances remain still unclear. In order to elucidate the functions of GPATCH4, we examined the effects of its dysfunction on cellular proliferation, alterations in nucleolar architecture, apoptotic events, and cellular senescence. Through experimentation conducted on cultured neuroblastoma SH-SY5Y cells, the reduction of GPATCH4 caused inhibition of cellular proliferation, concurrently fostering escalated apoptotic susceptibilities upon exposure to high-dose etoposide. In the realm of nucleolar morphology comparisons, a discernible decline was noted in the count of nucleoli per nucleus, concomitant with a significant expansion in the area occupied by individual nucleoli. Upon induction of senescence prompted by low-dose etoposide, GPATCH4 knockdown resulted in decreased cell viability and increased expression of senescence-associated markers, namely senescence-associated β-galactosidase (SA-β-GAL) and p16. Furthermore, GPATCH4 dysfunction elicited alterations in the gene expression profile of the ribosomal system. In sum, our findings showed that GPATCH4 is a pivotal nucleolar protein that regulates nucleolar morphology and is correlated with cell viability.

    DOI: 10.1016/j.bbrc.2023.149384

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  • Phosphorylation of α-synuclein at T64 results in distinct oligomers and exerts toxicity in models of Parkinson's disease. 国際誌

    Hideaki Matsui, Shinji Ito, Hideki Matsui, Junko Ito, Ramil Gabdulkhaev, Mika Hirose, Tomoyuki Yamanaka, Akihide Koyama, Taisuke Kato, Maiko Tanaka, Norihito Uemura, Noriko Matsui, Sachiko Hirokawa, Maki Yoshihama, Aki Shimozawa, Shin-Ichiro Kubo, Kenji Iwasaki, Masato Hasegawa, Ryosuke Takahashi, Keisuke Hirai, Akiyoshi Kakita, Osamu Onodera

    Proceedings of the National Academy of Sciences of the United States of America   120 ( 23 )   e2214652120   2023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)  

    α-Synuclein accumulates in Lewy bodies, and this accumulation is a pathological hallmark of Parkinson's disease (PD). Previous studies have indicated a causal role of α-synuclein in the pathogenesis of PD. However, the molecular and cellular mechanisms of α-synuclein toxicity remain elusive. Here, we describe a novel phosphorylation site of α-synuclein at T64 and the detailed characteristics of this post-translational modification. T64 phosphorylation was enhanced in both PD models and human PD brains. T64D phosphomimetic mutation led to distinct oligomer formation, and the structure of the oligomer was similar to that of α-synuclein oligomer with A53T mutation. Such phosphomimetic mutation induced mitochondrial dysfunction, lysosomal disorder, and cell death in cells and neurodegeneration in vivo, indicating a pathogenic role of α-synuclein phosphorylation at T64 in PD.

    DOI: 10.1073/pnas.2214652120

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  • Loss of GBA in zebrafish leads to dopaminergic neurodegeneration, but overexpression of α-synuclein does not further worsen degeneration. 国際誌

    Kazuki Kodera, Noriko Matsui, Akihiko Saitoh, Hideaki Matsui

    Neuroreport   33 ( 7 )   320 - 325   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)  

    OBJECTIVES: Parkinson's disease is a neurodegenerative disorder that causes motor and nonmotor symptoms due to the loss of dopaminergic nerves and is characterized by the presence of Lewy bodies, which are mainly composed of α-synuclein. Glucosylceramidase beta (GBA), which is a causative gene of autosomal recessive Gaucher disease, is also known to be a risk gene for Parkinson's disease. In this study, we tried to detect synergistic effects of α-synuclein accumulation and gba depletion on dopaminergic neurodegeneration in zebrafish. METHODS: We generated a transgenic line of zebrafish overexpressing the A53T α-synuclein and gba mutant fish, and analyzed pathologies of α-synuclein aggregation and neurodegeneration. RESULTS: Zebrafish overexpressing the A53T α-synuclein did not exhibit α-synuclein aggregate formation. After the loss of gba function in this mutant α-synuclein transgenic line, we observed the marked presence of α-synuclein aggregates. Loss of gba function in zebrafish resulted in dopaminergic and noradrenergic neurodegeneration but this level of neurodegeneration was not exacerbated by overexpression of mutant α-synuclein. CONCLUSIONS: These results indicate that loss of gba function was sufficient to generate a neurodegenerative phenotype in zebrafish regardless of the expression of α-synuclein.

    DOI: 10.1097/WNR.0000000000001788

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  • Evaluation of Ectopic Mitochondrial DNA in HeLa Cells

    Mohammad T. Hussan, Noriko Matsui, Hideaki Matsui

    Current Issues in Molecular Biology   44 ( 3 )   1215 - 1223   2022年3月

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    掲載種別:研究論文(学術雑誌)  

    The presence of ectopic DNA in the cytoplasm induces inflammation and cell death. It has been widely reported that leakage of nuclear DNA into the cytoplasm can mainly be sensed by cyclic GMP-AMP synthase (cGAS). We recently reported that mitochondria-derived cytoplasmic double-stranded DNA (dsDNA) that has escaped lysosomal degradation induces significant cytotoxicity in cultured cells and in vivo. Cytoplasmic mitochondrial DNA is assumed to be involved in various diseases and disorders, and more and more papers have been published confirming this. On the other hand, the current method for evaluating mitochondrial DNA in the cytoplasm may not be quantitative. Here, we introduce in detail a method to evaluate ectopic mitochondrial DNA in cells. This method is useful in basic research as well as in the study of aging, Parkinson’s disease, Alzheimer’s disease, heart failure, autoimmune diseases, cancer, and other conditions.

    DOI: 10.3390/cimb44030080

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  • Cytosolic dsDNA of mitochondrial origin induces cytotoxicity and neurodegeneration in cellular and zebrafish models of Parkinson’s disease

    Hideaki Matsui, Junko Ito, Noriko Matsui, Tamayo Uechi, Osamu Onodera, Akiyoshi Kakita

    Nature Communications   12 ( 1 )   2021年12月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    <title>Abstract</title>Mitochondrial dysfunction and lysosomal dysfunction have been implicated in Parkinson’s disease (PD), but the links between these dysfunctions in PD pathogenesis are still largely unknown. Here we report that cytosolic dsDNA of mitochondrial origin escaping from lysosomal degradation was shown to induce cytotoxicity in cultured cells and PD phenotypes in vivo. The depletion of PINK1, GBA and/or ATP13A2 causes increases in cytosolic dsDNA of mitochondrial origin and induces type I interferon (IFN) responses and cell death in cultured cell lines. These phenotypes are rescued by the overexpression of DNase II, a lysosomal DNase that degrades discarded mitochondrial DNA, or the depletion of IFI16, which acts as a sensor for cytosolic dsDNA of mitochondrial origin. Reducing the abundance of cytosolic dsDNA by overexpressing human DNase II ameliorates movement disorders and dopaminergic cell loss in gba mutant PD model zebrafish. Furthermore, IFI16 and cytosolic dsDNA puncta of mitochondrial origin accumulate in the brain of patients with PD. These results support a common causative role for the cytosolic leakage of mitochondrial DNA in PD pathogenesis.

    DOI: 10.1038/s41467-021-23452-x

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    その他リンク: http://www.nature.com/articles/s41467-021-23452-x

  • Degeneration of dopaminergic neurons and impaired intracellular trafficking in Atp13a2 deficient zebrafish. 国際誌

    Hiromi Nyuzuki, Shinji Ito, Keisuke Nagasaki, Yohei Nitta, Noriko Matsui, Akihiko Saitoh, Hideaki Matsui

    IBRO reports   9   1 - 8   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)  

    ATP13A2 is the autosomal recessive causative gene for juvenile-onset Parkinson's disease (PARK9, Parkinson's disease 9), also known as Kufor-Rakeb syndrome. The disease is characterized by levodopa-responsive Parkinsonism, supranuclear gaze palsy, spasticity, and dementia. Previously, we have reported that Atp13a2 deficient medaka fish showed dopaminergic neurodegeneration and lysosomal dysfunction, indicating that lysosome-autophagy impairment might be one of the key pathogeneses of Parkinson's disease. Here, we established Atp13a2 deficient zebrafish using CRISPR/Cas9 gene editing. We found that the number of TH + neurons in the posterior tuberculum and the locus coeruleus significantly reduced (dopaminergic neurons, 64 % at 4 months and 37 % at 12 months, p < 0.001 and p < 0.05, respectively; norepinephrine neurons, 52 % at 4 months and 40 % at 12 months, p < 0.001 and p < 0.05, respectively) in Atp13a2 deficient zebrafish, proving the degeneration of dopaminergic neurons. In addition, we found the reduction (60 %, p < 0.05) of cathepsin D protein expression in Atp13a2 deficient zebrafish using immunoblot. Transmission electron microscopy analysis using middle diencephalon samples from Atp13a2 deficient zebrafish showed lysosome-like bodies with vesicle accumulation and fingerprint-like structures, suggesting lysosomal dysfunction. Furthermore, a significant reduction (p < 0.001) in protein expression annotated with vesicle fusion with Golgi apparatus in Atp13a2 deficient zebrafish by liquid-chromatography tandem mass spectrometry suggested intracellular trafficking impairment. Therefore, we concluded that Atp13a2 deficient zebrafish exhibited degeneration of dopaminergic neurons, lysosomal dysfunction and the possibility of intracellular trafficking impairment, which would be the key pathogenic mechanism underlying Parkinson's disease.

    DOI: 10.1016/j.ibror.2020.05.002

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  • Cerebrospinal fluid injection into adult zebrafish for disease research. 国際誌

    Hideaki Matsui, Noriko Matsui

    Journal of neural transmission (Vienna, Austria : 1996)   124 ( 12 )   1627 - 1633   2017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)  

    A modified method of cerebrospinal fluid injection was developed for the efficient and reliable administration of substances to the zebrafish central nervous system. The accuracy of this modified method was evaluated using Alexa Fluor dye injection. A high survival ratio was achieved due to the simplicity of the procedure and ice-tricaine combined anaesthesia. To validate this new method, we injected ammonium chloride, which successfully blocked lysosome function resulting in elevated LC3-II and the accumulation of ubiquitinated proteins. Injection of human α-synuclein fibrils initiated a prion-like propagation of α-synuclein pathology in zebrafish. This method can be used to investigate the effects of various substances and the propagation of α-synuclein in the central nervous system.

    DOI: 10.1007/s00702-017-1787-7

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