Updated on 2025/06/26

Information

 

写真a

 
AMAGAI YUTA
 
Organization
Medical Institute of Bioregulation Department of Molecular and Structural Biology Assistant Professor
Graduate School of Systems Life Sciences Department of Systems Life Sciences（Concurrent）
Title
Assistant Professor
Contact information
メールアドレス
Tel
0926426833
Profile
哺乳類細胞の小胞体・ゴルジ体におけるタンパク質品質管理機構の解明 初期分泌経路における亜鉛イオン制御機構とその生理的意義の解明
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Research Areas

  • Life Science / Cell biology

  • Life Science / Functional biochemistry

Degree

  • Ph.D. (Life sciences)

Research History

  • Kyushu University Medical Institute of Bioregulation Assistant Professor 

    2024.4 - Present

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  • Tohoku University Institute of Multidisciplinary Research for Advanced Materials Division of Organic- and Bio-materials Research Researcher 

    2015.4 - 2024.3

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    Country：Japan

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  • 東北大学（助教（年俸制）） 2016.4–2024.3 東北大学（研究支援者） 2015.4–2016.3   

Education

  • Tohoku University   大学院　生命科学研究科   分子生命科学専攻　博士後期課程

    2011.4 - 2015.3

  • Tohoku University   大学院　生命科学研究科   分子生命科学専攻　博士前期課程

    2009.4 - 2011.3

  • Tohoku University   理学部   生物学科

    2005.4 - 2009.3

Research Interests・Research Keywords

  • Research theme： Molecular mechanisms of the regulation of zinc homeostasis in the early secretory pathway mediated by zinc transporters

    Keyword： zinc transporter, endoplasmic reticulum, Golgi apparatus, zinc

    Research period： 2019.4

  • Research theme： Molecular mechanisms of the regulation of ERp44 in the early secretory pathway

    Keyword： ERp44, endoplasmic reticulum, Golgi apparatus, pH, zinc

    Research period： 2015.4

Awards

  • 優秀演題賞（基礎領域）

    2023.8   日本亜鉛栄養治療研究会  

  • 優秀演題賞（基礎領域）

    2023.8   日本亜鉛栄養治療研究会  

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  • Metallomics Poster Prize

    2019.9   International Society for Zinc Biology   Metallomics Poster Prize

Papers

  • Zinc homeostasis governed by Golgi-resident ZnT family members regulates ERp44-mediated proteostasis at the ER-Golgi interface Reviewed International journal

    Yuta Amagai, Momo Yamada, Toshiyuki Kowada, Tomomi Watanabe, Yuyin Du, Rong Liu, Satoshi Naramoto, Satoshi Watanabe, Junko Kyozuka, Tiziana Anelli, Tiziana Tempio, Roberto Sitia, Shin Mizukami, Kenji Inaba

    Nature Communications   14 ( 1 )   2683 - 2683   2023.5   （ eISSN:2041-1723 ）

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Nature Communications  

    Many secretory enzymes acquire essential zinc ions (Zn2+) in the Golgi complex. ERp44, a chaperone operating in the early secretory pathway, also binds Zn2+ to regulate its client binding and release for the control of protein traffic and homeostasis. Notably, three membrane transporter complexes, ZnT4, ZnT5/ZnT6 and ZnT7, import Zn2+ into the Golgi lumen in exchange with protons. To identify their specific roles, we here perform quantitative Zn2+ imaging using super-resolution microscopy and Zn2+-probes targeted in specific Golgi subregions. Systematic ZnT-knockdowns reveal that ZnT4, ZnT5/ZnT6 and ZnT7 regulate labile Zn2+ concentration at the distal, medial, and proximal Golgi, respectively, consistent with their localization. Time-course imaging of cells undergoing synchronized secretory protein traffic and functional assays demonstrates that ZnT-mediated Zn2+ fluxes tune the localization, trafficking, and client-retrieval activity of ERp44. Altogether, this study provides deep mechanistic insights into how ZnTs control Zn2+ homeostasis and ERp44-mediated proteostasis along the early secretory pathway.

    DOI： 10.1038/s41467-023-38397-6

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  • Zinc regulates ERp44-dependent protein quality control in the early secretory pathway Reviewed

    Satoshi Watanabe, Yuta Amagai, Sara Sannino, Tiziana Tempio, Tiziana Anelli, Manami Harayama, Shoji Masui, Ilaria Sorrentino, Momo Yamada, Roberto Sitia, Kenji Inaba

    Nature Communications   10 ( 1 )   2019.12

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    Language：Others   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41467-019-08429-1

  • Development of luciferase-based highly sensitive reporters that detect ER-associated protein biogenesis abnormalities

    Kadokura, H; Harada, N; Yamaki, S; Hirai, N; Tsukuda, R; Azuma, K; Amagai, Y; Nakamura, D; Yanagitani, K; Taguchi, H; Kohno, K; Inaba, K

    ISCIENCE   27 ( 11 )   111189   2024.11   （ eISSN:2589-0042 ）

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    Language：English   Publisher：iScience  

    Localization to the endoplasmic reticulum (ER) and subsequent disulfide bond formation are crucial processes governing the biogenesis of secretory pathway proteins in eukaryotes. Hence, comprehending the mechanisms underlying these processes is important. Here, we have engineered firefly luciferase (FLuc) as a tool to detect deficiencies in these processes within mammalian cells. To achieve this, we introduced multiple cysteine substitutions into FLuc and targeted it to the ER. The reporter exhibited FLuc activity in response to defects in protein localization or disulfide bond formation within the ER. Notably, this system exhibited outstanding sensitivity, reproducibility, and convenience in detecting abnormalities in these processes. We applied this system to observe a protein translocation defect induced by an inhibitor of HIV receptor biogenesis. Moreover, utilizing the system, we showed that modulating LMF1 levels dramatically impacted the ER's redox environment, confirming that LMF1 plays some critical role in the redox control of the ER.

    DOI： 10.1016/j.isci.2024.111189

    Web of Science

    Scopus

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  • Zinc homeostasis governed by Golgi-resident ZnT family members regulates ERp44-mediated proteostasis at the ER-Golgi interface (vol 14, 2683, 2023)

    Amagai, Y; Yamada, M; Kowada, T; Watanabe, T; Du, YY; Liu, R; Naramoto, S; Watanabe, S; Kyozuka, J; Anelli, T; Tempio, T; Sitia, R; Mizukami, S; Inaba, K

    NATURE COMMUNICATIONS   14 ( 1 )   3466   2023.6   （ eISSN:2041-1723 ）

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    Language：English   Publisher：Nature Communications  

    The original version of this article contained a duplication of Supplementary Fig. 1 in the Supplementary Information. The Supplementary Information file has been corrected.

    DOI： 10.1038/s41467-023-39273-z

    Web of Science

    Scopus

    PubMed

  • Organelle-Level Labile Zn2+ Mapping Based on Targetable Fluorescent Sensors Reviewed

    Rong Liu, Toshiyuki Kowada, Yuyin Du, Yuta Amagai, Toshitaka Matsui, Kenji Inaba, Shin Mizukami

    ACS Sensors   7 ( 3 )   748 - 757   2022.3   （ ISSN:2379-3694 eISSN:2379-3694 ）

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    Language：Others   Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society ({ACS})  

    DOI： 10.1021/acssensors.1c02153

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  • A unique leucine-valine adhesive motif supports structure and function of protein disulfide isomerase P5 via dimerization Reviewed

    Masaki Okumura, Shingo Kanemura, Motonori Matsusaki, Misaki Kinoshita, Tomohide Saio, Dai Ito, Chihiro Hirayama, Hiroyuki Kumeta, Mai Watabe, Yuta Amagai, Young-Ho Lee, Shuji Akiyama, Kenji Inaba

    Structure   2021.4

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    Language：Others   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.str.2021.03.016

  • Quantitative Imaging of Labile Zn2+ in the Golgi Apparatus Using a Localizable Small-Molecule Fluorescent Probe Reviewed International journal

    Toshiyuki Kowada, Tomomi Watanabe, Yuta Amagai, Rong Liu, Momo Yamada, Hiroto Takahashi, Toshitaka Matsui, Kenji Inaba, Shin Mizukami

    Cell Chemical Biology   27 ( 12 )   1521 - 1531   2020.9

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    Language：English   Publishing type：Research paper (scientific journal)  

    Fluorescent Zn2+ probes used for the quantitative analysis of labile Zn2+ concentration ([Zn2+]) in target organelles are crucial for understanding the role of Zn2+ in biological processes. Although several fluorescent Zn2+ probes have been developed to date, there is still a lack of consensus concerning the [Zn2+] in intracellular organelles. In this study, we describe the development of ZnDA-1H, a small-molecule fluorescent probe for Zn2+, which exhibits less pH sensitivity, high Zn2+ selectivity, and large fluorescence enhancement upon binding to Zn2+. Through protein labeling technology, ZnDA-1H was precisely targeted in various intracellular organelles, such as the nucleus, mitochondria, endoplasmic reticulum, and Golgi apparatus. ZnDA-1H exhibited a reversible fluorescence response toward labile Zn2+ in these organelles in live cells. Using this probe, the [Zn2+] in the Golgi apparatus was estimated to be 25 ± 1 nM, suggesting that labile Zn2+ plays a physiological role in the secretory pathway.

    DOI： 10.1016/j.chembiol.2020.09.003

  • The Highly Dynamic Nature of ERdj5 Is Key to Efficient Elimination of Aberrant Protein Oligomers through ER-Associated Degradation Reviewed

    Ken-ichi Maegawa, Satoshi Watanabe, Kentaro Noi, Masaki Okumura, Yuta Amagai, Michio Inoue, Ryo Ushioda, Kazuhiro Nagata, Teru Ogura, Kenji Inaba

    Structure   25 ( 6 )   846 - 857.e4   2017.6

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    Language：Others   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.str.2017.04.001

  • Preparation of Selenoinsulin as a Long‐Lasting Insulin Analogue

    Kenta Arai, Toshiki Takei, Masaki Okumura, Satoshi Watanabe, Yuta Amagai, Yuya Asahina, Luis Moroder, Hironobu Hojo, Kenji Inaba, Michio Iwaoka

    Angewandte Chemie International Edition   56 ( 20 )   5522 - 5526   2017.5

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    Language：Others   Publishing type：Research paper (scientific journal)  

    DOI： 10.1002/anie.201701654

  • Rabin8 suppresses autophagosome formation independently of its guanine nucleotide-exchange activity towards Rab8 Reviewed

    Amagai Yuta, Itoh Takashi, Fukuda Mitsunori, Kensaku Mizuno

    The journal of biochemistry   158 ( 2 )   139 - 153   2015.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    Rabin8 suppresses autophagosome formation independently of its guanine nucleotide-exchange activity towards Rab8

    DOI： 10.1093/jb/mvv032

  • NDR2-mediated Rabin8 phosphorylation is crucial for ciliogenesis by switching binding specificity from phosphatidylserine to Sec15 Reviewed International journal

    Shuhei Chiba, Yuta Amagai, Yuta Homma, Mitsunori Fukuda, Kensaku Mizuno

    The EMBO Journal   32 ( 6 )   874 - 885   2013.2

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    Language：English   Publishing type：Research paper (scientific journal)  

    Primary cilia are antenna-like sensory organelles protruding from the plasma membrane. Defects in ciliogenesis cause diverse genetic disorders. NDR2 was identified as the causal gene for a canine ciliopathy, early retinal degeneration, but its role in ciliogenesis remains unknown. Ciliary membranes are generated by transport and fusion of Golgi-derived vesicles to the pericentrosome, a process requiring Rab11-mediated recruitment of Rabin8, a GDP-GTP exchange factor (GEF) for Rab8, and subsequent Rab8 activation and Rabin8 binding to Sec15, a component of the exocyst that mediates vesicle tethering. This study shows that NDR2 phosphorylates Rabin8 at Ser-272 and defects in this phosphorylation impair preciliary membrane assembly and ciliogenesis, resulting in accumulation of Rabin8-/Rab11-containing vesicles at the pericentrosome. Rabin8 binds to and colocalizes with GTP-bound Rab11 and phosphatidylserine (PS) on pericentrosomal vesicles. The phospho-mimetic S272E mutation of Rabin8 decreases affinity for PS but increases affinity for Sec15. These results suggest that NDR2-mediated Rabin8 phosphorylation is crucial for ciliogenesis by triggering the switch in binding specificity of Rabin8 from PS to Sec15, thereby promoting local activation of Rab8 and ciliary membrane formation.

    DOI： 10.1038/emboj.2013.32

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Presentations

  • 過剰亜鉛が引き起こす小胞体レドックス恒常性の破綻 Invited

    天貝 佑太

    レドックスR&D戦略委員会シンポジウム  2025.3 

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    Event date： 2025.3

    Language：Japanese   Presentation type：Oral presentation (invited, special)  

    Venue：東京  

  • ZIP7 controls zinc concentration and redox state in the ER International conference

    Yuta Amagai, Kenji Inaba

    The 8th ISZB Meeting 

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    Event date： 2024.12

    Language：English   Presentation type：Oral presentation (general)  

    Venue：Merida   Country：Mexico  

  • Zn2+ has a potential to regulate the redox homeostasis of the ER by inhibiting Ero1α activity Invited

    天貝 佑太, 稲葉 謙次.

    第97回日本生化学会年会 

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    Event date： 2024.11

    Language：English   Presentation type：Oral presentation (invited, special)  

    Venue：横浜  

  • 亜鉛イオンとの結合を介したERp44による分泌経路中のタンパク質品質管理機構

    天貝佑太, 渡部 聡, 原山麻奈美, 増井翔史, SaraSannino, Roberto Sitia, 稲葉謙次

    第69回日本細胞生物学会大会  2017.6 

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    Language：Japanese  

  • 亜鉛イオンはERp44によるタンパク質品質管理機構を制御する

    天貝佑太, 渡部聡, 原山麻奈美, 山田桃, Sara Sannino, Roberto Sitia, 稲葉謙次

    2017年度生命科学系学会合同年次大会  2017.12 

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    Language：Japanese  

  • 亜鉛が制御する初期分泌経路のタンパク質品質管理機構

    天貝佑太、山田桃、渡邊朝美、小和田俊行、渡部聡、水上進、稲葉謙次

    第19回日本蛋白質科学会年会　第71回日本細胞生物学会大会　合同年次大会  2019.6 

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    Language：Japanese  

  • ZnT7 regulates ERp44 through the control of Zn2+ concentrations at the ERGIC/cis-Golgi Invited

    Yuta Amagai, Momo Yamada, Tomomi Watanabe, Toshiyuki Kowada, Satoshi Naramoto, Satoshi Watanabe, Junko Kyozuka, Roberto Sitia, Shin Mizukami, Kenji Inaba

    第４２回日本分子生物学会年会  2019.12 

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    Language：English  

  • 哺乳動物細胞分泌経路における亜鉛調節とタンパク質品質管理 Invited

    天貝佑太、山田桃、渡邊朝美、小和田俊行、楢本悟史、渡部聡、経塚淳子、Roberto Sitia、水上進、稲葉謙次

    第62回　日本植物生理学会年会  2021.3 

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    Language：Japanese  

  • 初期分泌経路における亜鉛濃度制御が小胞体―ゴルジ体シャペロンERp44の機能をコントロールする Invited

    天貝佑太、山田桃、渡邊朝美、小和田俊行、楢本悟史、渡部聡、経塚淳子、Roberto Sitia、水上進、稲葉謙次

    第21回　日本蛋白質科学会年会  2021.6 

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    Language：Japanese  

  • ZIP7 regulates the physiological function of ERp44

    Chihiro Arai, Yuta Amagai, Kenji Inaba

    第44回　日本分子生物学会年会  2021.12 

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    Language：English  

  • 小胞体における亜鉛とレドックスのクロストークの新規メカニズムの発見 Invited

    天貝佑太，新井千尋、稲葉謙次

    第2回　レドックスR&D戦略委員会春のシンポジウム  2022.3 

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    Language：Japanese  

  • ERp44を介した亜鉛とレドックスホメオスタシスのクロストーク Invited

    天貝佑太，新井千尋、稲葉謙次

    第22回　日本蛋白質科学会年会  2022.6 

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    Language：Japanese  

  • Close linkage between redox and zinc homeostasis in the endoplasmic reticulum Invited International conference

    Yuta Amagai, Chihiro Arai, Kenji Inaba

    Redox Week in Sendai 2022  2022.10 

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    Language：English  

  • 亜鉛が制御する分泌経路内タンパク質品質管理機構 Invited

    天貝 佑太, 稲葉 謙次

    第34回日本微量元素学会学術集会  2023.9 

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    Language：Japanese  

  • 小胞体における亜鉛とレドックスのクロストーク Invited

    天貝 佑太, 稲葉 謙次

    メタルバイオサイエンス研究会2023  2023.10 

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    Language：Japanese  

  • Zinc homeostasis in the ER is crucial for proteostasis of the early secretory pathway Invited

    Yuta Amagai, Kenji Inaba

    第46回日本分子生物学会年会  2023.12 

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    Language：English  

  • 生命金属科学の深化-バイオメタル研究の新展開-　亜鉛が制御する分泌経路内タンパク質品質管理機構

    天貝 佑太, 稲葉 謙次

    Biomedical Research on Trace Elements  2023.9  (一社)日本微量元素学会

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    Language：Japanese  

  • 亜鉛が制御する分泌経路内タンパク質品質管理機構(Protein quality control systems in the early secretory pathway regulated by zinc ions)

    Amagai Yuta, Inaba Kenji

    Metallomics Research  2023.12  (一社)日本微量元素学会

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    Language：English  

  • ケミカルプロテオスタシス:タンパク質品質管理におけるレドックスと金属イオンの協奏　Zn2+はEro1α活性を阻害することでERの酸化還元ホメオスタシスを制御する可能性がある(Zn2+ has a potential to regulate the redox homeostasis of the ER by inhibiting Ero1α activity)

    天貝 佑太, 稲葉 謙次

    日本生化学会大会プログラム・講演要旨集  2024.11  (公社)日本生化学会

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    Language：English  

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MISC

  • 亜鉛イオンの結合が制御するタンパク質品質管理の新たなメカニズム Invited

    天貝佑太, 稲葉謙次

    生体の科学   75 ( 2 )   138 - 142   2024.4

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    Authorship：Lead author   Language：Japanese   Publisher：医学書院  

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  • 【生命現象を駆動する生体内金属動態の理解と展開】タンパク質を機能化する生体内での金属挿入メカニズム　亜鉛イオンが制御するタンパク質品質管理の新たなメカニズム

    天貝 佑太, 稲葉 謙次

    生体の科学   75 ( 2 )   138 - 142   2024.4   （ ISSN:0370-9531 ）

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    Language：Japanese   Publisher：(公財)金原一郎記念医学医療振興財団  

    ＜文献概要＞亜鉛は必須微量元素であり,生体内で多くのタンパク質と相互作用し多様な機能を持つ。細胞内および各オルガネラ内の遊離亜鉛イオン濃度([Zn2+])は,多くの亜鉛輸送体膜タンパク質によって調節されると考えられているが,その詳細については不明な点が多い。本稿では,筆者らが最近解明した,ゴルジ体における亜鉛恒常性維持機構と,それによって制御される初期分泌経路タンパク質品質管理について紹介する。

  • 初期分泌経路における新たなタンパク質品質管理機構 ---亜鉛イオンとERp44の協奏

    天貝佑太, 渡部聡, 稲葉謙次

    実験医学   2020.3

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    Language：Japanese  

  • 細胞周期と高次な生命現象とのかかわり 8.一次繊毛形成と細胞周期のクロストーク

    千葉秀平, 天貝佑太, 水野健作

    実験医学   2013.2

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    Language：Japanese  

    細胞周期と高次な生命現象とのかかわり 8.一次繊毛形成と細胞周期のクロストーク

Professional Memberships

  • The molecular biology society of Japan

Research Projects

  • 新規小胞体亜鉛制御機構の同定とその生理機能解明

    Grant number：25K00102  2025.4 - 2028.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    天貝 佑太

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    Grant type：Scientific research funding

    亜鉛は必須微量元素であり、多様な生命現象に関与するため、細胞・オルガネラ内の亜鉛恒常性維持機構の破綻は疾病の原因となる。小胞体に亜鉛が異常に蓄積すると、小胞体ストレスとコラーゲン合成不全を引き起こすが、その分子機序は未解明である。また、小胞体亜鉛濃度を制御する分子機構はほとんど不明である。
    本研究では、小胞体亜鉛がレドックス分子を制御する機構、小胞体へ亜鉛を流出入する機構、小胞体亜鉛の蓄積がコラーゲン生合成を阻害する機序をそれぞれ分子から細胞のレベルで詳細に解明することを目指す。

    CiNii Research

  • 小胞体亜鉛を制御する新規分子機構の探索

    2024.4 - 2027.3

    公益財団　旭硝子財団  化学・生命分野 若手継続グラント

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    Authorship：Principal investigator  Grant type：Donation

  • 高時空間分解能解析によるゴルジ体亜鉛制御とエクトエンザイム活性化機構の解明

    Grant number：22H04797  2022 - 2023

    Japan Society for the Promotion of Science・Ministry of Education, Culture, Sports, Science and Technology  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

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    Grant type：Scientific research funding

  • 分泌経路内の亜鉛が制御するタンパク質品質管理機構の解明

    Grant number：21K06060  2021 - 2023

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Grant type：Scientific research funding

  • ZIP亜鉛輸送体による初期分泌経路の亜鉛制御とその機能解明

    2021

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    Grant type：Donation

  • 初期分泌経路への亜鉛流入機構と亜鉛酵素活性化機構の解明

    Grant number：20H05494  2020 - 2021

    Japan Society for the Promotion of Science・Ministry of Education, Culture, Sports, Science and Technology  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

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    Authorship：Principal investigator  Grant type：Scientific research funding

  • 細胞生物学とケミカルバイオロジーの融合による初期分泌経路の亜鉛イオン動態の解明

    2020

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    Grant type：Donation

  • 亜鉛輸送体とERp44による初期分泌経路タンパク質品質管理機構の解明

    Grant number：19K16065  2019 - 2020

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Early-Career Scientists

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    Grant type：Scientific research funding

  • 分泌経路におけるERp44を介したタンパク質品質管理機構とその生理的意義の解明

    Grant number：17K15085  2017 - 2018

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists(A)or(B)

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    Grant type：Scientific research funding

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Educational Activities

  • システム生命学府生命医科学特論Ｉを一部担当

Class subject

  • 生命医科学特論Ｉ

    2024.4 - 2024.9   First semester

  • 生命医科学特論Ⅰ

    2025.6 - 2025.8   Summer quarter

  • Topics in medical life sciences Ⅰ

    2025.6 - 2025.8   Summer quarter

  • Topics in medical life sciences Ⅰ

    2024.6 - 2024.8   Summer quarter

  • 生命医科学特論Ⅰ

    2024.6 - 2024.8   Summer quarter