2022/07/05 更新

写真a

ハネ マサヤ
羽根 正弥
HANE Masaya
所属
糖鎖生命コア研究所 統合生命医科学糖鎖研究センター 分子生理・動態部門 助教
大学院生命農学研究科 助教
大学院担当
大学院生命農学研究科
職名
助教

学位 1

  1. 博士(農学) ( 2016年3月   名古屋大学 ) 

研究分野 1

  1. ライフサイエンス / 応用生物化学

経歴 6

  1. 名古屋大学   糖鎖生命コア研究所   助教

    2021年9月 - 現在

  2. 名古屋大学   大学院生命農学研究科   助教

    2021年6月 - 現在

  3. 名古屋大学   大学院生命農学研究科   特任助教

    2020年4月 - 2021年5月

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    国名:日本国

  4. 名古屋大学   大学院生命農学研究科   研究員

    2020年1月 - 2020年3月

  5. 名古屋大学   生物機能開発利用研究センター   研究員

    2019年2月 - 2019年12月

  6. University of California, San Diego   Cellular and Molecular Medicine   研究員

    2016年9月 - 2019年1月

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学歴 2

  1. 名古屋大学   生命農学研究科   生命技術科学専攻

    2011年4月 - 2016年3月

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    国名: 日本国

  2. 名古屋大学   農学部   応用生命科学科

    2007年4月 - 2011年3月

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    国名: 日本国

所属学協会 3

  1. 日本糖質学会

  2. 日本生化学会

  3. 日本農芸化学会

受賞 1

  1. 第2回日本糖質学会優秀講演賞受賞者

    2019年8月   日本糖質学会   統合失調症患者に見出される ST8SIA2 のプロモーター領域 rSNP のインパクトの解析

 

論文 14

  1. The α2,8-sialyltransferase 6 (St8sia6) localizes in the ER and enhances the anchorage-independent cell growth in cancer.

    Hatanaka R, Araki E, Hane M, Go S, Wu D, Kitajima K, Sato C

    Biochemical and biophysical research communications   608 巻   頁: 52 - 58   2022年3月

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    記述言語:英語   出版者・発行元:Biochemical and Biophysical Research Communications  

    Sialylation, the final stage of post-translational modification of proteins, is achieved in the Golgi apparatus and is related to the malignant phenotype of cancer. Disialylation of ganglioside (GD3) by St8sia1 and polysialylation by St8sia2 and 4 have been shown to be related to malignant phenotypes; however, di/oligosialylation by St8sia6 is still unknown. In this study, we analyzed the malignant phenotype of St8sia6 and found that upregulation of St8sia6 in melanoma B16 cells increased anchorage-independent cell growth, which was not due to sialic acid cleavage by a sialidase. Moreover, unlike other sialyltransferases, St8sia6 localized to the endoplasmic reticulum (ER). We found that the localization to the Golgi apparatus could be regulated by swapping experiments using St8sia2; however, the malignant phenotype did not change. These data demonstrate that the enhancement of anchorage-independent cell growth by St8sia6 is not due to its localization of ER, but is due to the expression of the protein itself.

    DOI: 10.1016/j.bbrc.2022.03.146

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  2. Analysis of biochemical features of ST8 alpha-N-acetyl-neuraminide alpha 2,8-sialyltransferase (St8sia) 5 isoforms

    Araki Erino, Hane Masaya, Hatanaka Rina, Kimura Ryota, Tsuda Kana, Konishi Miku, Komura Naoko, Ando Hiromune, Kitajima Ken, Sato Chihiro

    GLYCOCONJUGATE JOURNAL   39 巻 ( 2 ) 頁: 291 - 302   2022年1月

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    記述言語:日本語   出版者・発行元:Glycoconjugate Journal  

    Gangliosides are important components of the membrane and are involved in many biological activities. St8sia5 is an α2,8-sialyltransferase involved in ganglioside synthesis, and has three isoforms. In this study, we analyzed the features of three isoforms, St8sia5-S, -M, and -L that had not been analyzed, and found that only St8sia5-L was localized in the Golgi, while the majority of St8sia5-M and -S were localized in the ER. The localization of Golgi of St8sia5 depended on the stem region. In addition, the incorporation of exogenous GD3 was upregulated only in St8sia5-L expressing cells. Taken together, the localization of St8sia5 is important for the activity of the enzyme.

    DOI: 10.1007/s10719-021-10034-8

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  3. Lower promoter activity of the ST8SIA2 gene has been favored in evolving human collective brains

    Hayakawa Toshiyuki, Terahara Masahiro, Fujito Naoko T., Matsunaga Takumi, Teshima Kosuke M., Hane Masaya, Kitajima Ken, Sato Chihiro, Takahata Naoyuki, Satta Yoko

    PLOS ONE   16 巻 ( 12 ) 頁: e0259897   2021年12月

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    記述言語:日本語   出版者・発行元:PLoS ONE  

    ST8SIA2 is an important molecule regulating expression of the phenotype involved in schizophrenia. Lowered promoter activity of the ST8SIA2 gene is considered to be protective against schizophrenia by conferring tolerance to psychosocial stress. Here, we examined the promoter-type composition of anatomically modern humans (AMHs) and archaic humans (AHs; Neanderthals and Denisovans), and compared the promoter activity at the population level (population promoter activity; PPA) between them. In AMHs, the TCT-type, showing the second lowest promoter activity, was most prevalent in the ancestral population of non-Africans. However, the detection of only the CGT-type from AH samples and recombination tracts in AH sequences showed that the CGT- and TGT-types, exhibiting the two highest promoter activities, were common in AH populations. Furthermore, interspecies gene flow occurred into AMHs from AHs and into Denisovans from Neanderthals, influencing promoter-type compositions independently in both AMHs and AHs. The difference of promoter-type composition makes PPA unique in each population. East and Southeast Asian populations show the lowest PPA. This results from the selective increase of the CGC-type, showing the lowest promoter activity, in these populations. Every non-African population shows significantly lower PPA than African populations, resulting from the TCT-type having the highest prevalence in the ancestral population of non-Africans. In addition, PPA reduction is also found among subpopulations within Africa via a slight increase of the TCT-type. These findings indicate a trend toward lower PPA in the spread of AMHs, interpreted as a continuous adaptation to psychosocial stress arising in migration. This trend is considered as genetic tuning for the evolution of collective brains. The inferred promoter-type composition of AHs differed markedly from that of AMHs, resulting in higher PPA in AHs than in AMHs. This suggests that the trend toward lower PPA is a unique feature in AMH spread.

    DOI: 10.1371/journal.pone.0259897

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  4. Human-specific microglial Siglec-11 transcript variant has the potential to affect polysialic acid-mediated brain functions at a distance. 査読有り 国際誌

    Hane M, Chen DY, Varki A

    Glycobiology   31 巻 ( 3 ) 頁: 231 - 242   2021年4月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/glycob/cwaa082

    PubMed

  5. Comparative Studies of Polysialic Acids Derived from Five Different Vertebrate Brains 国際誌

    Yang Yi, Murai Ryo, Takahashi Yuka, Mori Airi, Hane Masaya, Kitajima Ken, Sato Chihiro

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   21 巻 ( 22 ) 頁: 1 - 22   2020年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:International Journal of Molecular Sciences  

    Polysialic acid (polySia/PSA) is a linear homopolymer of sialic acid (Sia) that primarily modifies the neural cell adhesion molecule (NCAM) in mammalian brains. PolySia-NCAM not only displays an anti-adhesive function due to the hydration effect, but also possesses a molecule-retaining function via a direct binding to neurologically active molecules. The quality and quantity of polySia determine the function of polySia-NCAM and are considered to be profoundly related to the maintenance of normal brain functions. In this study, to compare the structures of polySia-NCAM in brains of five different vertebrates (mammals, birds, reptiles, amphibians, and fish), we adopted newly developed combinational methods for the analyses. The results revealed that the structural features of polySia considerably varied among different species. Interestingly, mice, as a mammal, possess eminently distinct types of polySia, in both quality and quantity, compared with those possessed by other animals. Thus, the mouse polySia is of larger quantities, of longer and more diverse chain lengths, and of a larger molecular size with higher negative charge, compared with polySia of other species. These properties might enable more advanced brain function. Additionally, it is suggested that the polySia/Sia ratio, which likely reflects the complexity of brain function, can be used as a new promising index to evaluate the intelligence of different vertebrate brains.

    DOI: 10.3390/ijms21228593

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  6. Combinational Analyses with Multiple Methods Reveal the Existence of Several Forms of Polysialylated Neural Cell Adhesion Molecule in Mouse Developing Brains 査読有り 国際誌

    Mori Airi, Yang Yi, Takahashi Yuka, Hane Masaya, Kitajima Ken, Sato Chihiro

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   21 巻 ( 16 ) 頁: 1 - 20   2020年8月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:International Journal of Molecular Sciences  

    Polysialic acid (polySia/PSA) is an anionic glycan polymer of sialic acid, and it mostly modifies the neural cell adhesion molecule (NCAM) in mammalian brains. Quality and quantity of the polySia of the polySia–NCAM is spatio-temporally regulated in normal brain development and functions, and their impairments are reported to be related to diseases, such as psychiatric disorders and cancers. Therefore, precise understanding of the state of polySia–NCAM structure would lead to the diagnosis of diseases for which their suitable evaluation methods are necessary. In this study, to develop these evaluation methods, structures of polySia–NCAM from mouse brains at six different developmental stages were analyzed by several conventional and newly developed methods. Integrated results of these experiments clearly demonstrated the existence of different types of polySia–NCAMs in developing brains. In addition, combinational analyses were shown to be useful for precise understanding of the quantity and quality of polySia, which can provide criteria for the diagnosis of diseases.

    DOI: 10.3390/ijms21165892

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  7. Acute stress-induced change in polysialic acid levels mediated by sialidase in mouse brain 査読有り

    Abe Chikara, Yi Yang, Hane Masaya, Kitajima Ken, Sato Chihiro

    SCIENTIFIC REPORTS   9 巻 ( 1 ) 頁: 9950   2019年7月

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    記述言語:日本語   出版者・発行元:Scientific Reports  

    Stress is an important environmental factor influencing human behaviour and causing several mental disorders. Alterations in the structure of polysialic acid (polySia/PSA) due to genetic alterations in ST8SIA2, which encodes a polySia-synthesizing enzyme, are related to certain mental disorders. However, whether stress as an environmental factor leads to changes in polySia structure is unknown. Here we studied the effects of acute stress on polySia expression and found reductions in both the quantity and quality of polySia in the olfactory bulb and prefrontal cortex, even with short-term exposure to acute stress. The use of inhibitors for sialidase, microglia and astrocytes revealed that these declines were due to a transient action of sialidase from microglia and astrocytes in the olfactory bulb and prefrontal cortex, respectively. These data suggest that sialidase dynamically regulates polySia expression in a brain region-specific manner.

    DOI: 10.1038/s41598-019-46240-6

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  8. Mental disorders and an acidic glycan-from the perspective of polysialic acid (PSA/polySia) and the synthesizing enzyme, ST8SIA2 査読有り

    Sato Chihiro, Hane Masaya

    GLYCOCONJUGATE JOURNAL   35 巻 ( 4 ) 頁: 353 - 373   2018年8月

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    記述言語:日本語   出版者・発行元:Glycoconjugate Journal  

    Mental disorders, such as schizophrenia, bipolar disorder, and autism spectrum disorder, are challenging to manage, worldwide. Understanding the molecular mechanisms underlying these disorders is essential and required. Studies investigating such molecular mechanisms are well performed and important findings are accumulating apace. Based on the fact that these disorders are due in part to the accumulation of genetic and environmental risk factors, consideration of multi-molecular and/or multi-system dependent phenomena might be important. Acidic glycans are an attractive family of molecules for understanding these disorders, because impairment of the fine-tuned glycan system affects a large number of molecules that are deeply involved in normal brain function. One of the candidates of this important family of glycan epitopes in the brain is polysialic acid (PSA/polySia). PSA is a well-known molecule because of its role as an oncodevelopmental antigen and is also widely used as a marker of adult neurogenesis. Recently, several reports have suggested that PSA and PSA-related genes are associated with multiple mental disorders. The relationships among PSA, PSA-related genes, and mental disorders are reviewed here.

    DOI: 10.1007/s10719-018-9832-9

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  9. Positive selection on schizophrenia-associated ST8SIA2 gene in post-glacial Asia 査読有り

    Fujito Naoko T., Satta Yoko, Hane Masaya, Matsui Atsushi, Yashima Kenta, Kitajima Ken, Sato Chihiro, Takahata Naoyuki, Hayakawa Toshiyuki

    PLOS ONE   13 巻 ( 7 ) 頁: e0200278   2018年7月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PLoS ONE  

    A number of loci are associated with highly heritable schizophrenia and the prevalence of this mental illness has had considerable negative fitness effects on human populations. Here we focused on one particular schizophrenia-associated gene that encodes a sialyltransferase (ST8SIA2) and is expressed preferentially in the brain with the level being largely determined by three SNPs in the promoter region. It is suggested that the expression level of the ST8SIA2 gene is a genetic determinant of schizophrenia risk, and we found that a geographically differentiated non-risk SNP type (CGC-type) has significantly reduced promoter activity. A newly developed method for detecting ongoing positive selection was applied to the ST8SIA2 genomic region with the identification of an unambiguous sweep signal in a rather restricted region of 18 kb length surrounding the promoter. We also found that while the CGC-type emerged in anatomically modern humans in Africa over 100 thousand years ago, it has increased its frequency in Asia only during the past 20–30 thousand years. These findings support that the positive selection is driven by psychosocial stress due to changing social environments since around the last glacial maximum, and raise a possibility that schizophrenia extensively emerged during the Upper Paleolithic and Neolithic era.

    DOI: 10.1371/journal.pone.0200278

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  10. Different properties of polysialic acids synthesized by the polysialyltransferases ST8SIA2 and ST8SIA4 査読有り

    Mori Airi, Hane Masaya, Niimi Yuki, Kitajima Ken, Sato Chihiro

    GLYCOBIOLOGY   27 巻 ( 9 ) 頁: 834 - 846   2017年9月

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

    Polysialic acid (polySia) is mainly found as a modification of neural cell adhesion molecule (NCAM) in whole embryonic brains, as well as restricted areas of adult vertebrate brains, including the hippocampus. PolySia shows not only repulsive effects on NCAM-involved cell–cell interactions due to its bulky and hydrated properties, but also attractive effects on the interaction with neurologically active molecules, which exerts a reservoir function. Two different polysialyltransferases, ST8SIA2 and ST8SIA4, are involved in the synthesis of polySia chains; however, to date, the differences of the properties between polySia chains synthesized by these two enzymes remain unknown. In this study, to clarify this point, we first prepared polySia-NCAMs from HEK293 cells stably expressing ST8SIA4 and ST8SIA2, or ST8SIA2 (SNP-7), a mutant ST8SIA2 derived from a schizophrenia patient. The conventional sensitive chemical and immunological characterizations showed that the quantity and quality (structural features) of polySia are not so much different between ST8SIA4- and ST8SIA2-synthesized ones, apart from those of ST8SIA2 (SNP-7). Then, we assessed the homophilic and heterophilic interactions mediated by polySia-NCAM by adopting a surface plasmon resonance measurement as an in vitro analytical method. Our novel findings are as follows: (i) the ST8SIA2- and ST8SIA4-synthesized polySia-NCAMs exhibited different attractive and repulsive effects than each other; (ii) both polySia- and oligoSia-NCAMs synthesized by ST8SIA2 were able to bind polySia-NCAMs; (iii) the polySia-NCAM synthesized by a ST8SIA2 (SNP-7) showed markedly altered attractive and repulsive properties. Collectively, polySia-NCAM is suggested to simultaneously possess both attractive and repulsive properties that are highly regulated by the two polysialyltransferases.

    DOI: 10.1093/glycob/cwx057

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  11. Chlorpromazine Increases the Expression of Polysialic Acid (PolySia) in Human Neuroblastoma Cells and Mouse Prefrontal Cortex 査読有り

    Abe Chikara, Nishimura Saki, Mori Airi, Niimi Yuki, Yang Yi, Hane Masaya, Kitajima Ken, Sato Chihiro

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   18 巻 ( 6 )   2017年6月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:International Journal of Molecular Sciences  

    The neural cell adhesion molecule (NCAM) is modified by polysialic acid (polySia or PSA) in embryonic brains. In adult brains, polySia modification of NCAM is only observed in restricted areas where neural plasticity, remodeling of neural connections, or neural generation is ongoing although the amount of NCAM remains unchanged. Impairments of the polySia-expression and several single nucleotide polymorphisms (SNPs) of the polysialyltransferase (polyST) ST8SIA2 gene are reported to be associated with schizophrenia and bipolar disorder. Chlorpromazine (CPZ) is well-known as an agent for treating schizophrenia, and our hypothesis is that CPZ may affect the polySia expression or the gene expression of polySTs or NCAM. To test this hypothesis, we analyzed the effects of CPZ on the expression of polySia-NCAM on human neuroblastoma cell line, IMR-32 cells, by immunochemical and chemical methods. Interestingly, the cell surface expression of polySia, especially those with lower chain lengths, was significantly increased on the CPZ-treated cells, while mRNAs for polySTs and NCAM, and the amounts of total polySia-NCAM remained unchanged. The addition of brefeldin A, an inhibitor of endocytosis, suppressed the CPZ-induced cell surface polySia expression. In addition, polySia-NCAM was also observed in the vesicle compartment inside the cell. All these data suggest that the level of cell surface expression of polySia in IMR-32 is highly regulated and that CPZ changes the rate of the recycling of polySia-NCAM, leading to the up-regulation of polySia-NCAM on the cell surface. We also analyzed the effect of CPZ on polySia-expression in various brain regions in adult mice and found that CPZ only influenced the total amounts of polySia-NCAM in prefrontal cortex. These results suggest a brain-region-specific effect of CPZ on the expression of total polySia in mouse brain. Collectively, anti-schizophrenia agent CPZ consistently up-regulates the expression polySia at both cellular and animal levels.

    DOI: 10.3390/ijms18061123

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  12. Polysialyltransferase ST8SIA2 and psychiatric disorders

    Hane M., Kitajima K., Sato C.

    Seikagaku   89 巻 ( 5 ) 頁: 634 - 643   2017年

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    記述言語:日本語   出版者・発行元:Seikagaku  

    DOI: 10.14952/SEIKAGAKU.2017.890634

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  13. ポリシアル酸転移酵素遺伝子ST8SIA2と精神疾患の関わり 査読有り

    羽根正弥, 北島 健, 佐藤 ちひろ

    生化学   89 巻   頁: 634 - 643   2017年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

  14. ポリシアル酸転移酵素遺伝子ST8SIA2と精神疾患の関わり 査読有り

    羽根 正弥, 佐藤 ちひろ

    生化学   89 巻   頁: 634 - 643   2017年

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書籍等出版物 1

  1. Role of Polysialic Acid in Schizophrenia

    Sato C., Hane M., Kitajima K.

    Comprehensive Glycoscience: Second Edition  2021年6月  ( ISBN:9780128222447

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    記述言語:日本語

    DOI: 10.1016/B978-0-12-819475-1.00026-2

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科研費 1

  1. 免疫細胞レクチンシグレックの新規リガンド結合部位の証明と新しい免疫制御機構の解明

    研究課題/研究課題番号:21H02425  2021年4月 - 2025年3月

    科学研究費助成事業  基盤研究(B)

    佐藤 ちひろ, 呉 迪, 田中 浩士, 長江 雅倫, 羽根 正弥

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    担当区分:研究分担者 

    免疫応答は病原体や異物、がんなどの変異した細胞から身体を守る重要な生体防御機構である。自然免疫において、免疫細胞上で活躍する分子群としてレクチン(糖鎖認識分子)が存在する。レクチンは特に糖鎖を介した自己・非自己の認識に長けており、シグレックは細胞表面のシアル酸を自己と認識し、免疫細胞の活性化抑制に関わることが知られている。しかしそのリガンド認識メカニズムは不明な点が多い。本研究は、申請者が初めてSiglec上にその存在を発見した新規シアル酸結合領域Site2に着目し、リガンド結合の構造基盤の解明、natural ligandの同定、リガンド認識制御メカニズムの解明を目指すものである。