Researcher Database
| Hiromi Watari |
| Faculty of Fisheries Sciences Marine Life Science Marine Bioresources Chemistry |
| Assistant Professor |
Last Updated :2024/05/09
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- 30962758
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Educational Organization
- Bachelor's degree program School of Fisheries Sciences
- Master's degree program Graduate School of Fisheries Sciences
- Doctoral (PhD) degree program Graduate School of Fisheries Sciences
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Published Papers
- Ryuichi Sakai, Ken Matsumura, Hajime Uchimasu, Kei Miyako, Tohru Taniguchi, V Raghavendra Rao Kovvuri, Anjana Delpe Acharige, Kenneth G Hull, Daniel Romo, Lakkana Thaveepornkul, Sarin Chimnaronk, Hiroko Miyamoto, Ayato Takada, Hiromi Watari, Masaki J Fujita, Jiro SakaueThe Journal of organic chemistry 2024/04/01Mellpaladines A-C (1-3) and dopargimine (4) are dopamine-derived guanidine alkaloids isolated from a specimen of Palauan Didemnidae tunicate as possible modulators of neuronal receptors. In this study, we isolated the dopargimine derivative 1-carboxydopargimine (5), three additional mellpaladines D-F (6-8), and serotodopalgimine (9), along with a dimer of serotonin, 5,5'-dihydroxy-4,4'-bistryptamine (10). The structures of these compounds were determined based on spectrometric and spectroscopic analyses. Compound 4 and its congeners dopargine (11), nordopargimine (15), and 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)ethan-1-amine (16) were synthetically prepared for biological evaluations. The biological activities of all isolated compounds were evaluated in comparison with those of 1-4 using a mouse behavioral assay upon intracerebroventricular injection, revealing key functional groups in the dopargimines and mellpaladines for in vivo behavioral toxicity. Interestingly, these alkaloids also emerged during a screen of our marine natural product library aimed at identifying antiviral activities against dengue virus, SARS-CoV-2, and vesicular stomatitis Indiana virus (VSV) pseudotyped with Ebola virus glycoprotein (VSV-ZGP).
- Kenji Morokuma, Hiromi Watari, Maika Mori, Ryuichi Sakai, Raku Irie, Masato OikawaTetrahedron 133623 - 133623 0040-4020 2023/08
- Interaction of Polyamine-modified Marine Peptide Aculeine A with Cell Membranes: Disruption or EntryHiromi Watari, Reimi Kishi, Satoko Matsunaga, Takayuki Nishikawa, Yuji Sawada, Akito Honda, Masaki J Fujita, Ryuichi SakaiChemistry Letters 52 (3) 185 - 189 0366-7022 2023/03/05 [Refereed]
- Hiromi Watari, Hiromu Kageyama, Nami Masubuchi, Hiroya Nakajima, Kako Onodera, Pamela J. Focia, Takumi Oshiro, Takashi Matsui, Yoshio Kodera, Tomohisa Ogawa, Takeshi Yokoyama, Makoto Hirayama, Kanji Hori, Douglas M. Freymann, Misa Imai, Norio Komatsu, Marito Araki, Yoshikazu Tanaka, Ryuichi SakaiNature Communications 13 (1) 7262 - 7262 2022/11/25 [Refereed]
Abstract N-glycan-mediated activation of the thrombopoietin receptor (MPL) under pathological conditions has been implicated in myeloproliferative neoplasms induced by mutant calreticulin, which forms an endogenous receptor-agonist complex that traffics to the cell surface and constitutively activates the receptor. However, the molecular basis for this mechanism is elusive because oncogenic activation occurs only in the cell-intrinsic complex and is thus cannot be replicated with external agonists. Here, we describe the structure and function of a marine sponge-derived MPL agonist, thrombocorticin (ThC), a homodimerized lectin with calcium-dependent fucose-binding properties. In-depth characterization of lectin-induced activation showed that, similar to oncogenic activation, sugar chain-mediated activation persists due to limited receptor internalization. The strong synergy between ThC and thrombopoietin suggests that ThC catalyzes the formation of receptor dimers on the cell surface. Overall, the existence of sugar-mediated MPL activation, in which the mode of activation is different from the original ligand, suggests that receptor activation is unpredictably diverse in living organisms. - Hiromi Watari, Hiromu Kageyama, Nami Masubuchi, Hiroya Nakajima, Kako Onodera, Pamela Focia, Takumi Oshiro, Takashi Matsui, Yoshio Kodera, Tomohisa Ogawa, Takeshi Yokoyama, Makoto Hirayama, Kanji Hori, Douglas Freymann, Norio Komatsu, Marito Araki, Yoshikazu Tanaka, Ryuichi Sakai2022/04/01
- Hiromi Watari, Hiromu Kageyama, Nami Masubuchi, Hiroya Nakajima, Kako Onodera, Pamela J. Focia, Takumi Oshiro, Takashi Matsui, Yoshio Kodera, Tomohisa Ogawa, Takeshi Yokoyama, Makoto Hirayama, Kanji Hori, Douglas M. Freymann, Norio Komatsu, Marito Araki, Yoshikazu Tanaka, Ryuichi Sakai2021/10/29ABSTRACT N-glycan-mediated activation of the thrombopoietin receptor (MPL) under pathological conditions has been implicated in myeloproliferative neoplasms induced by mutant calreticulin, which forms an endogenous receptor-agonist complex that constitutively activates the receptor. However, the molecular basis for this mechanism has not been studied because no external agonists existed. We describe the structure and function of a marine sponge-derived MPL agonist, thrombocorticin (ThC), a homodimerized lectin with calcium-dependent fucose-binding properties. ThC-induced activation persists due to limited receptor internalization. The strong synergy between ThC and thrombopoietin suggests that ThC catalyzes the formation of receptor dimers on the cell surface. MPL is subject to sugar-mediated activation, where the kinetics differ from those of cytokines. This result suggests the presence of diverse receptor activation pathways in human thrombopoiesis. One-sentence summary A marine sponge lectin catalyzes thrombopoietin receptor dimerization and activation, exhibiting strong synergy with thrombopoietin, and modulates internalization of the receptor.
- Hiromi Watari, Hiroya Nakajima, Wataru Atsuumi, Takanori Nakamura, Takeshi Nanya, Yuji Ise, Ryuichi SakaiComparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 221 82 - 88 1532-0456 2019/07 [Refereed]
MISC
- Cytological effects of a novel sponge derived protein toxin, soritesidineHiromi Watari, Masaya Kitano, Yuri Ishibashi, Ryuichi Sakai The 38th Symposium on Natural Products 2023/10
- MECHANISM OF CYTOKINE RECEPTOR ACTIVATION BY MARINE SPONGE LECTINHiromi Watari, Hiroki Kageyama, Nami Masubuchi, Marito Araki, Yoshikazu Tanaka, Ryuichi Sakai ECMNP-MaNaPro 2023 2023/09
- 受容体の新規活性化機構を掘り起こす海洋天然物辺浩美 第１５回化学生態学研究会 2023/06 [Invited]
- 海綿由来レクチン ThC によるサイトカイン受容体 新規活性化機構の解明令和4年度 日本農芸化学会 北海道・東北支部 合同支部会 2022/09
- 海綿由来レクチンをプローブとしたサイトカイン受容体 新規活性化機構の解明第64回天然有機化合物討論会 2022/09
- Activation of thrombopoietin receptor by sponge derived protein: A Novel mechanism of activation of c-MplPacifichem 2021 2021/12
- 辺浩美, 影山大夢, 中島寛弥, 小野寺かこ, 増渕菜弥, 大城拓未, 松井崇, 小寺義男, 小川智久, 平山真, 堀貫治, 横山武司, 小松則夫, 小松則夫, 荒木真理人, 荒木真理人, 田中良和, 酒井隆一 日本血液学会学術集会抄録(Web) 83rd- 2021
Research Grants & Projects
- Sugar mediated activation of cytokine receptor by marine sponge-derived lectinJapan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity Start-upDate (from‐to) : 2022/08 -2024/03Author : 辺 浩美
- Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for JSPS FellowsDate (from‐to) : 2020/04 -2022/03Author : 辺 浩美トロンボコルチシン（ThC）はミクロネシア産海綿Corticium sp.から得られた新規タンパク質である。ThCは血小板分化に関わるサイトカイン、トロンボポエチン（TPO）の受容体に作用しTPOと類似した活性を示したが、その詳細は不明であった。 今年度の本研究では、ThCはどのようにTPO受容体へ作用しているのか？この疑問の答えの一端を捉えることができた。 本研究ではまず、ThCのアミノ酸配列を決定した。Edman分解とMS/MSによるペプチドマスマッピングを用いて全配列を推定したところ、アミノ酸131残基のタンパク質であることが明らかとなった。ThCのアミノ酸配列はTPOとの類似性が無い一方で、バクテリア由来のレクチンと相同性を持つことが分かった。レクチンとは糖と結合するタンパク質の総称である。この結果からThCと糖との結合性を調べたところ、フコースとマンノースに親和性を持ち、細胞培養液にThCと同時に添加するとThCの活性が著しく阻害された。さらに、X線結晶構造解析の結果からThCはフコースとマンノースとの共結晶が得られている。したがって、ThCはTPO受容体の糖鎖に結合することで、活性を発揮しているのではないかという仮説が生じた。