Updated on 2024/03/21
博士（学術） （ 2003.3 東京大学 ）
Cellular signal transduction
Calcium
Nutrients
mTOR
Life Science / Applied biochemistry / Molecular Cell Biology
動物細胞における栄養シグナル応答の分子細胞生物学的研究
日本学術振興会特別研究員PD
2008.4 - 2011.3
Country：Japan
日本学術振興会特別研究員DC2
2002.4 - 2004.3
Country：Japan
The University of Tokyo Graduate School, Division of General Culture
1998.4 - 2003.3
Country： Japan
Tokyo Institute of Technology Faculty of Life Science and Engineering
1994.4 - 1998.3
Country： Japan
日本分子生物学会
日本農芸化学会
日本生化学会
日本細胞生物学会
Top Downloaded Papers of IJMS in 2023
2023 President & Publisher MDPI New Insights into the Regulation of mTOR Signaling via Ca2+-Binding Proteins
Yuna Amemiya, Masatoshi Maki, Hideki Shibata, Terunao Takahara
16th FAOBMB Poster Awards
2002 Federation of Asian and Oceanian Biochemists and Molecular Biologists
New Insights into the Regulation of mTOR Signaling via Ca(2+)-Binding Proteins. Reviewed
Amemiya Y, Maki M, Shibata H, Takahara T
International journal of molecular sciences Vol. 24 ( 4 ) 2023.2
Roles of phosphatidylserine and phospholipase C in the activation of TOR complex 2 signaling in Saccharomyces cerevisiae. Reviewed
Nomura W, Ng SP, Takahara T, Maeda T, Kawada T, Goto T, Inoue Y
Journal of cell science Vol. 135 ( 17 ) 2022.9
Amino Acid-Mediated Intracellular Ca2+ Rise Modulates mTORC1 by Regulating the TSC2-Rheb Axis through Ca2+/Calmodulin Reviewed
Amemiya Yuna, Nakamura Nao, Ikeda Nao, Sugiyama Risa, Ishii Chiaki, Maki Masatoshi, Shibata Hideki, Takahara Terunao
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol. 22 ( 13 ) 2021.7
The Novel ALG-2 Target Protein CDIP1 Promotes Cell Death by Interacting with ESCRT-I and VAPA/B Reviewed
Inukai Ryuta, Mori Kanako, Kuwata Keiko, Suzuki Chihiro, Maki Masatoshi, Takahara Terunao, Shibata Hideki
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol. 22 ( 3 ) 2021.2
The Penta-EF-Hand ALG-2 Protein Interacts with the Cytosolic Domain of the SOCE Regulator SARAF and Interferes with Ubiquitination
Zhang Wei, Muramatsu Ayaka, Matsuo Rina, Teranishi Naoki, Kahara Yui, Takahara Terunao, Shibata Hideki, Maki Masatoshi
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol. 21 ( 17 ) 2020.9
Amino acid-dependent control of mTORC1 signaling: a variety of regulatory modes Invited Reviewed
Takahara Terunao, Amemiya Yuna, Sugiyama Risa, Maki Masatoshi, Shibata Hideki
JOURNAL OF BIOMEDICAL SCIENCE Vol. 27 ( 1 ) page： 87 2020.8
High Sensitive Quantitative Binding Assays Using a Nanoluciferase-Fused Probe for Analysis of ALG-2-Interacting Proteins.
Zhang W, Matsuo R, Takahara T, Shibata H, Maki M
Methods in molecular biology (Clifton, N.J.) Vol. 1929 page： 501 - 516 2019
Cellular Ca<sup>2+</sup>-Responding Nanoluciferase Reporter Gene System Directed by Tandemly Repeated Pseudo-palindromic NFAT-Response Elements.
Zhang W, Takahara T, Achiha T, Shibata H, Maki M
Methods in molecular biology (Clifton, N.J.) Vol. 1929 page： 95 - 109 2019
Takahara Terunao, Arai Yumika, Kono Yuta, Shibata Hideki, Maki Masatoshi
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Vol. 497 ( 2 ) page： 492 - 498 2018.3
Nanoluciferase Reporter Gene System Directed by Tandemly Repeated Pseudo-Palindromic NFAT-Response Elements Facilitates Analysis of Biological Endpoint Effects of Cellular Ca2+ Mobilization
Zhang Wei, Takahara Terunao, Achiha Takuya, Shibata Hideki, Maki Masatoshi
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol. 19 ( 2 ) 2018.2
The calcium-binding protein ALG-2 regulates protein secretion and trafficking via interactions with MISSL and MAP1B proteins. Reviewed
Takahara T, Inoue K, Arai Y, Kuwata K, Shibata H, Maki M.
J. Biol. Chem. Vol. 292 page： 17057-17072 2017.10
The calcium-binding protein ALG-2 promotes endoplasmic reticulum exit site localization and polymerization of Trk-fused gene (TFG) protein. Reviewed
Kanadome T, Shibata H, Kuwata K, Takahara T, Maki M.
FEBS J. Vol. 284 ( 1 ) page： 56-76 2017.1
The calcium-binding protein ALG-2 promotes endoplasmic reticulum exit site localization and polymerization of Trk-fused gene (TFG) protein
Kanadome Takashi, Shibata Hideki, Kuwata Keiko, Takahara Terunao, Maki Masatoshi
FEBS JOURNAL Vol. 284 ( 1 ) page： 56-76 2017.1
Multifaceted Roles of ALG-2 in Ca(2+)-Regulated Membrane Trafficking. Reviewed
Masatoshi Maki, Terunao Takahara, Hideki Shibata
Int. J. Mol. Sci. Vol. 17 ( 9 ) page： E1401 (1-23) 2016.8
Tubby-like protein superfamily member PLSCR3 functions as a negative regulator of adipogenesis in mouse 3T3-L1 preadipocytes by suppressing induction of late differentiation stage transcription factors. Reviewed
Akira Inokawa, Tatsuyoshi Inuzukam Terunao Takahara, Hideki Shibata, and Masatoshi Maki
Bioscience Reports Vol. 36 page： e00287 2016
Structural Analysis of the Complex between Penta-EF-Hand ALG-2 Protein and Sec31A Peptide Reveals a Novel Target Recognition Mechanism of ALG-2 Reviewed
Takeshi Takahashi, Kyousuke Kojima, Wei Zhang, Kanae Sasaki, Masaru Ito, Hironori Suzuki, Masato Kawasaki, Soichi Wakatsuki, Terunao Takahara, Hideki Shibata, Masatoshi Maki
International Journal of Molecular Sciences Vol. 16 page： 3677-3699 2015.2
Involvement of calpain-7 in epidermal growth factor receptor degradation via the endosomal sorting pathway. Reviewed
Maemoto, Y., Ono, Y., Kiso, S., Shibata, H., Takahara, T., Sorimachi, H., and Maki, M.
FEBS Journal Vol. 281 page： 3642-3655 2014
Evolutionary conserved regulation of TOR signaling. Invited Reviewed
Terunao Takahara, Tatsuya Maeda
Journal of Biochemistry Vol. 154 page： 1-10 2013
ストレス刺激に応答したTOR複合体1(TORC1)の活性制御機構 Invited Reviewed
高原照直, 前田達哉
生化学 Vol. 85 ( 3 ) page： 205-213 2013
Hyper-activation of the target of rapamycin (Tor) kinase 1 decreases intracellular glutathione content in Sacchromyces cerevisiae as revealed by LC-MS/MS analysis. Reviewed
Masahide Oku, Yayoi Ichiki, Akiko Shiraishi, Terunao Takahara, Tatsuya Maeda, Yasuyoshi Sakai
Bioscience, Biotechnology, and Biochemistry Vol. 77 page： 1608-1611 2013
Changes in cell morphology are coodinated with cell growth through the TORC1 pathway. Reviewed
Alexi I Goranov, Amneet Gulati, Noah Dephoure, Terunao Takahara, Tatsuya Maeda, Steven P Gygi, Scott Manalis, Angelika Amon
Current Biology Vol. 23 page： 1269-1279 2013
Nuclear ALG-2 protein interacts with Ca2+ Homeostasis Endoplasmic Reticulum Protein (CHERP) Ca2+-dependently and participates in regulation of alternative splicing of inositol trisphosphate receptor typeI (IP3R1) pre-mRNA. Reviewed
Kanae Sasaki-Osugi, Chiaki Imoto, Terunao Takahara, Hideki Shibata, Masatoshi Maki
Journal of Biological Chemistry Vol. 288 page： 33361-33375 2013
Transient sequestration of TORC1 into stress granules. Reviewed
Terunao Takahara, Tatsuya Maeda
Molecular Cell Vol. 47 page： 242-252 2012
Stress granule: the last refuge of TORC1? Invited Reviewed
Terunao Takahara, Tatsuya Maeda
Vol. 11 page： 3707-3708 2012
Sphingolipids regulate the yeast high osmolarity-responsive HOG pathway. Reviewed
Mirai Tanigawa, Akio Kihara, Minoru Terashima, Terunao Takahara, Tatsuya Maeda
Molecular and Cellular Biology Vol. 32 page： 2861-2870 2012
TORC1 activity of fission yeast is rapamycin-sensitive. Reviewed
Terunao Takahara, Tatsuya Maeda
Genes to Cells Vol. 17 page： 698-708 2012
Endocytosis of the aspartic acid/glutamic acid transporter Dip5 is triggered by substrate-dependent recruitment of the Rsp5 ubiquitin ligase via the arrestin-like protein Aly2. Reviewed
Riko Hatakeyama, Masao Kamiya, Terunao Takahara, Tatsuya Maeda
Molecular and Cellular Biology Vol. 30 page： 5598-5607 2010
Evaluation of mTOR function by a gain-of-function approach. Invited Reviewed
Yoichiro Ohne, Terunao Takahara, Tatsuya Maeda
Cell Cycle Vol. 8 page： 573-579 2009
mTOR阻害薬 Invited Reviewed
髙原照直、前田達哉
腎と透析 Vol. 67 ( 5 ) page： 697 - 613 2009
Isolation of hyperactive mutants of mammalian target of rapamycin. Reviewed
Yoichiro Ohne, Terunao Takahara, Riko Hatakeyama, Tomoko Matsuzaki, Makoto Noda, Noboru Mizushima, Tatsuya Maeda
Journal of Biological Chemistry Vol. 283 page： 31861-31870 2008
Nutrient-dependent multimerization of the mammalian target of rapamycin through the N-terminal HEAT repeat region. Reviewed
Terunao Takahara, Kenta Hara, Kazuyoshi Yonezawa, Hiroyuki Sorimachi, Tatsuya Maeda
Journal of Biological Chemistry Vol. 281 page： 28605-28614 2006
Delay in synthesis of the 3' splice site promotes trans-splicing of the preceding 5' splice site. Reviewed
Terunao Takahara, Bosiljka Tasic, Tom Maniatis, Hiroshi Akanuma, Shuichi Yanagisawa
Molecular Cell Vol. 18 page： 245-251 2005
細胞内トランス-スプライシング Invited Reviewed
高原照直, 柳澤修一
生化学 Vol. 77 ( 12 ) page： 1501-1505 2005
The trans-spliced variants of Sp1 mRNA in rat. Reviewed
Terunao Takahara, Daisuke Kasahara, Daisuke Mori, Shuichi Yanagisawa, Hiroshi Akanuma
Biochemical Biophysical Research Communications Vol. 298 page： 156-162 2002
Heterogeneous Sp1 mRNAs in human HepG2 cells include a product of homotypic trans-splicing. Reviewed
Terunao Takahara, Shinichi Kanazu, Shuichi Yanagisawa, Hiroshi Akanuma
Journal of Biological Chemistry Vol. 275 page： 38067-38072 2000
mTORシグナル シグナル伝達キーワード事典
高原照直, 前田達哉（ Role： Joint author）
羊土社 2012
脂肪酸合成酵素によるmTORC1活性への影響
髙原照直
第13回TOR研究会 2023.11.11 TOR研究会
近接依存性ビオチン標識法を用いたRheb近傍因子の同定と解析
高原照直
第12回TOR研究会 2022.10.30 TOR研究会
Ca2+シグナルを介したTSC2-Rheb-mTORC1経路の制御 Invited
高原照直
第2回シロリムス新作用研究会 2021.10.23 JASMIN研究会
細胞成長制御を司る mTORC1 経路の新規制御因子の探索と同定
小林海咲
第190回日本農芸化学会中部支部例会 2021.9.18
アミノ酸応答シグナル経路におけるカルシウムを介した新規制御機構の解明
雨宮優奈
第190回日本農芸化学会中部支部例会 2021.9.18
動物細胞の成長制御を司るmTORC1経路のCa2+シグナルによる調節機構の解析
雨宮優奈
日本生化学会中部支部例会 2021.5.22
アミノ酸応答mTORC1シグナル経路のCa2+シグナルを介した制御機構 Invited
髙原照直
第43回日本分子生物学会 2020.12.2 日本分子生物学会
カルシウムシグナルによるTSC2-Rheb経路を介したmTORC1制御 Invited
髙原照直
第10回TOR研究会 2020.7.2 TOR研究会
アミノ酸応答性mTORC1活性化におけるカルシウムシグナルの意義 Invited
髙原照直
第9回TOR研究会 2019.6.27 TOR研究会
アミノ酸によるmTORC1活性化の 新規メカニズムの解析
髙原照直
2019年度日本農芸化学会 2019.3.26 日本農芸化学会
細胞のアミノ酸感知機構の最前線 Invited
髙原照直
東工大セミナー 2019.1.24 東京工業大学
アミノ酸依存的mTORC1活性化における細胞内カルシウムの役割の解析 Invited
髙原照直
第8回TOR研究会 2018.6.29 TOR研究会
アミノ酸依存的mTORC1活性化における細胞内カルシウム濃度の役割 Invited
髙原照直
第7回TOR研究会 2017.9.25
アミノ酸は細胞内カルシウム濃度上昇を介して mTORC1経路を活性化する
髙原照直
2017年度日本農芸化学会 2017.3.18 日本農芸化学会
Analysis of amino acids-induced mTORC1 activation through intracellular calcium rise Invited
Terunao Takahara
2016.12.1
細胞内カルシウム上昇を介したアミノ酸依存的mTORC1活性化機構 Invited
髙原照直
第6回TOR研究会 2016.9.30 TOR研究会
TORC1 regulation mediated by stress granule formation upon heat stress
Grant number：22K05440 2022.4 - 2025.3
科学研究費助成事業 基盤研究(C)
高原 照直
Authorship：Principal investigator
Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）
動物細胞の成長や恒常性維持には、タンパク質合成、脂質合成などを司るmTOR（mammalian/mechanistic Target Of Rapamycin）キナーゼが深く関わっている。近年、Ca2+シグナル異常により発症する病的心肥大がmTOR経路異常と関連することも報告されており、Ca2+シグナルとmTOR経路との相互作用ネットワークの重要性が示唆されるが、その具体的な分子メカニズムは不明である。本研究では、Ca2+シグナルによるmTOR経路制御の仕組みと意義を解明し、関連する疾患の予防法創出に向けた基盤的知見を得ることを目指す。
Grant number：20K05837 2020.4 - 2023.3
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Authorship：Coinvestigator(s)
Analysis of intracellular signaling pathway regulated by amino acids
Grant number：17K07752 2017.4 - 2020.3
Takahara Terunao
Authorship：Principal investigator
Grant amount：\4810000 （ Direct Cost: \3700000 、 Indirect Cost：\1110000 ）
The purpose of this study was to analyze the role of calcium signaling in the mechanistic target of rapamycin complex 1 (mTORC1) pathway, which is known as a central role in response to amino acids. Our findings revealed that the increase in intracellular calcium concentration caused by amino acids was important for mTORC1 regulation. Furthermore, we analyzed how these calcium concentration fluctuations regulate the mTORC1 pathway, Our results suggested that calmodulin binds to TSC2 acting upstream of mTORC1 pathway and regulates mTORC1 activity.
Grant number：17H03803 2017.4 - 2020.3
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
MAKI Masatoshi
Authorship：Coinvestigator(s)
Ca2+ is a signaling molecule that plays important roles in eukaryotic cells.In order to investigate the physiological functions of Ca2+-binding protein ALG-2, we searched and identified four new ALG-2-interacting proteins.MISSL accumulates at endoplasmic reticulum (ER) exit sites with ALG-2 upon increase in cytosolic Ca2+ concentrations. It cooperates with microtubule associated protein 1B (MAP1B) to regulate vesicular transport of cargoes from the ER to the Golgi apparatus. ALG-2 binds single-pass ER transmembrane protein named SARAF and suppresses ubiquitination of SARAF. CDIP1 localizes at the endomembrane systems and binds a subset of ESCRT-I proteins in the presence of Ca2+/ALG-2 to promote cell death. We analyzed recruitment of ALG-2 to lysosomes upon impairment of lysosomal membranes. We established a new high sensitive Ca2+-response reporter gene assay system to monitor effects of Ca2+. The system is expected to apply to evaluate food constituents and drugs.
Elucidation and application of regulatory mechanisms underlying biogenesis of transport vesicles budding from the endoplasmic reticulum
Grant number：15K07384 2015.4 - 2018.3
Shibata Hideki
Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid)
In mammalian cells, proteins destined for secretion are transported from specialized region of the ER, called ER exit site (ERES), by COPII vesicles. The aim of this study was to investigate the role of ALG-2, a calcium-binding protein, in the regulation of COPII-mediated protein transport. ALG-2 directly interacts with Sec31A, an outer coat component of COPII. Firstly, we identified Trk-fused gene (TFG) product as a novel target for ALG-2. Overexpression of ALG-2 enhanced the localization of TFG to the ERES. Secondly, MISSL was shown to be recruited to the ERES by ALG-2 in response to calcium mobilization. We also found that ALG-2 bridged between MISSL and MAP1B. In our co-immunoprecipitation analysis, TFG, MISSL and MAP1B did not form the complex with Sec31A, suggesting that ALG-2 may have divergent functions at the ERES. Finally, we reported that amyotrophic lateral sclerosis (ALS)-associated mutations in annexin A11 caused abnonormality in binding to S100A6.
応用生命科学実験実習2
2014
情報リテラシー入門
2014
International Journao of Molecular Sciences Guest Editor
Role(s)：Supervision (editorial), Peer review
MDPI 2021.3 - 2021.12
