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Tsuji Takuma
| Institute for Genetic Medicine Disease Control | Specially Appointed Lecturer |
Researcher basic information
■ Degree■ URL
researchmap URLホームページURL■ Various IDs
Researcher number
- 40725628
- AAY-1249-2020
Research KeywordResearch Field
Career
■ CareerCareer
- Apr. 2023 - Present
Hokkaido University, Institute for Genetic Medicine, 特任講師 - Apr. 2019 - Mar. 2023
Juntendo University, Graduate School of Medicine, 特任助教 - Jul. 2014 - Mar. 2019
名古屋大学大学院, 医学系研究科 分子細胞学, 助教 - Jun. 2013 - Jun. 2014
Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 助教 - Apr. 2013 - May 2013
Nagoya University, Ecotopia Science Institute, 博士研究員
Research activity information
■ Awards- Mar. 2022, 日本解剖学会, 奨励賞
辻琢磨 - May 2015, 第71回日本顕微鏡学会学術講演会, 優秀ポスター賞
辻琢磨 - Feb. 2013, 名古屋大学材料バックキャストテクノロジー研究センター, 若手研究奨励賞
辻琢磨 - Nov. 2012, 2012 International Symposium on Micro-Nano Mechatronics and Human Science, Best Poster Award
辻琢磨 - Jul. 2012, 第6回ナノバイオメディカル学会大会, 若手優秀演題賞
辻琢磨 - Jul. 2012, 第28回日本DDS学会学術集会, 優秀発表者賞
辻琢磨 - Nov. 2011, The 7th International Forum on Oxidative Stress and Aging, The Popinigis' Doctoral Student Award
辻琢磨
- ATG deficiency impairs stationary-phase microlipophagy through acetic acid-induced clustering of Niemann–Pick type C proteins
Tsuji T.; Fujimoto M.; Noda N. N.; Fujimoto T.
bioRxiv, openRxiv, 26 Apr. 2026, [Lead author, Corresponding author]
Summary
While the role of autophagy-related (ATG) proteins in microautophagy remains unclear, their absence in budding yeast has been reported to impair stationary-phase microlipophagy. Here, we show that this defect in ATG-deficient ( atg Δ) cells arises not from a direct requirement of ATG proteins for the execution of microlipophagy but from accumulation of acetic acid (AA) in the medium. High concentrations of AA in the medium of atg Δ cells trigger the clustering of Niemann–Pick type C (NPC) proteins, causing impairment of raft-like vacuolar microdomain formation and suppression of microlipophagy. Lowering extracellular AA rapidly dissolves NPC protein clusters, restores vacuolar microdomains, and rescues microlipophagy in atg Δ cells. Conversely, elevating AA concentrations in the medium of wild-type cells induces NPC protein clusters and microlipophagy defects. These findings demonstrate that stationary-phase microlipophagy can proceed independently of ATG proteins and that the defect in atg Δ cells can be rescued by normalizing extracellular AA levels. - Reversible one-way lipid transfer at ER–autophagosome membrane contact sites via Atg2
Hao L.; Midorikawa T.; Ogasawara Y.; Tsuji T.; Kishimoto T.; Hama Y.; Lang H.; Noda NN; Suzuki K.
Journal of Cell Biology, 225, 5, Rockefeller University Press, 10 Mar. 2026, [Peer-reviewed]
Scientific journal, Bridge-like lipid transfer proteins (LTPs) contain a repeating β-groove domain and long hydrophobic grooves that act as bridges at membrane contact sites (MCSs) to efficiently transfer lipids. Atg2 is one such bridge-like LTP essential for autophagosome formation, during which a newly synthesized isolation membrane (IM) emerges and expands through lipid supply. However, studies on Atg2-mediated lipid transfer are limited to in vitro studies due to the lack of a suitable probe for monitoring phospholipid dynamics in vivo. Here, we characterized the lipophilic dye octadecyl rhodamine B (R18), which internalizes and labels the endoplasmic reticulum (ER) in a manner that requires flippases and oxysterol-binding protein–related proteins. Using R18, we demonstrated phospholipid transfer from the ER to the IM during autophagy in vivo. Upon autophagy termination, our data suggested the reversible phospholipid flow from the IM to the ER in response to environmental changes. Our findings highlight the critical role of bridge-like LTPs in MCS-mediated phospholipid homeostasis. - Phase separation promotes Atg8 lipidation and vesicle condensation for autophagy progression
Fujioka Y.; Tsuji T.; Kotani T.; Kumeta H.; Kakuta C.; Shimasaki J.; Fujimoto T.; Nakatogawa H.; Noda NN
Nature Structural & Molecular Biology, Springer Science and Business Media LLC, 16 Sep. 2025, [Peer-reviewed]
Scientific journal - Definition of phosphatidylinositol 4,5-bisphosphate distribution by freeze-fracture replica labeling
Takuma Tsuji; Junya Hasegawa; Takehiko Sasaki; Toyoshi Fujimoto
Journal of Cell Biology, 2025, [Peer-reviewed], [Lead author]
Scientific journal - Physicochemical properties of the vacuolar membrane and cellular factors determine formation of vacuolar invaginations
Kimura Y; Tsuji T; Shimizu Y; Watanabe Y; Kimura M; Fujimoto T; Higuchi M
Scientific Reports, 13, 1, Springer Science and Business Media LLC, 27 Sep. 2023, [Peer-reviewed]
Scientific journal, Abstract
Vacuoles change their morphology in response to stress. In yeast exposed to chronically high temperatures, vacuolar membranes get deformed and invaginations are formed. We show that phase-separation of vacuolar membrane occurred after heat stress leading to the formation of the invagination. In addition, Hfl1, a vacuolar membrane-localized Atg8-binding protein, was found to suppress the excess vacuolar invaginations after heat stress. At that time, Hfl1 formed foci at the neck of the invaginations in wild-type cells, whereas it was efficiently degraded in the vacuole in the atg8Δ mutant. Genetic analysis showed that the endosomal sorting complex required for transport machinery was necessary to form the invaginations irrespective of Atg8 or Hfl1. In contrast, a combined mutation with the vacuole BAR domain protein Ivy1 led to vacuoles in hfl1Δivy1Δ and atg8Δivy1Δ mutants having constitutively invaginated structures; moreover, these mutants showed stress-sensitive phenotypes. Our findings suggest that vacuolar invaginations result from the combination of changes in the physiochemical properties of the vacuolar membrane and other cellular factors. - Subcellular distribution of membrane lipids revealed by freeze-fracture electron microscopy
Tsuji T
Anatomical Science International, Springer Science and Business Media LLC, 14 Jun. 2023, [Peer-reviewed], [Lead author, Corresponding author]
Scientific journal - Characterization of micron-scale protein-depleted plasma membrane domains in phosphatidylserine-deficient yeast cells
Mioka T; Guo T; Wang S; Tsuji T; Kishimoto T; Fujimoto T; Tanaka K
Journal of Cell Science, 135, 5, The Company of Biologists, 01 Mar. 2022, [International Magazine]
English, Scientific journal,ABSTRACT
Membrane phase separation to form micron-scale domains of lipids and proteins occurs in artificial membranes; however, a similar large-scale phase separation has not been reported in the plasma membrane of the living cells. We show here that a stable micron-scale protein-depleted region is generated in the plasma membrane of yeast mutants lacking phosphatidylserine at high temperatures. We named this region the ‘void zone’. Transmembrane proteins and certain peripheral membrane proteins and phospholipids are excluded from the void zone. The void zone is rich in ergosterol, and requires ergosterol and sphingolipids for its formation. Such properties are also found in the cholesterol-enriched domains of phase-separated artificial membranes, but the void zone is a novel membrane domain that requires energy and various cellular functions for its formation. The formation of the void zone indicates that the plasma membrane in living cells has the potential to undergo phase separation with certain lipid compositions. We also found that void zones were frequently in contact with vacuoles, in which a membrane domain was also formed at the contact site. - Ultrastructural localization of de novo synthesized phosphatidylcholine in yeast cells by freeze-fracture electron microscopy
Tsuji T; Fujimoto T
STAR Protocols, 2, 4, 100990, 100990, Elsevier BV, Dec. 2021, [Peer-reviewed], [Lead author]
English, Scientific journal - Transmembrane phospholipid translocation mediated by Atg9 is involved in autophagosome formation
Orii M; Tsuji T#(co-first author); Ogasawara Y; Fujimoto T
Journal of Cell Biology, 2021, [Peer-reviewed], [Lead author]
Scientific journal, The mechanism of isolation membrane formation in autophagy is receiving intensive study. We recently found that Atg9 translocates phospholipids across liposomal membranes and proposed that this functionality plays an essential role in the expansion of isolation membranes. The distribution of phosphatidylinositol 3-phosphate in both leaflets of yeast autophagosomal membranes supports this proposal, but if Atg9-mediated lipid transport is crucial, symmetrical distribution in autophagosomes should be found broadly for other phospholipids. To test this idea, we analyzed the distributions of phosphatidylcholine, phosphatidylserine, and phosphatidylinositol 4-phosphate by freeze-fracture electron microscopy. We found that all these phospholipids are distributed with comparable densities in the two leaflets of autophagosomes and autophagic bodies. Moreover, de novo-synthesized phosphatidylcholine is incorporated into autophagosomes preferentially and shows symmetrical distribution in autophagosomes within 30 min after synthesis, whereas this symmetrical distribution is compromised in yeast expressing an Atg9 mutant. These results indicate that transbilayer phospholipid movement that is mediated by Atg9 is involved in the biogenesis of autophagosomes. - Atg9 is a lipid scramblase that mediates autophagosomal membrane expansion
Matoba K; Kotani T#; Tsutsumi A#; Tsuji T#(co-second author); Mori T; Noshiro D; Sugita Y; Nomura N; Iwata S; Ohsumi Y; Fujimoto T; Nakatogawa H; Kikkawa M; Noda N.N
Nature Structural & Molecular Biology, 27, 12, 1185, 1193, Springer Science and Business Media LLC, Dec. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, The molecular function of Atg9, the sole transmembrane protein in the autophagosome-forming machinery, remains unknown. Atg9 colocalizes with Atg2 at the expanding edge of the isolation membrane (IM), where Atg2 receives phospholipids from the endoplasmic reticulum (ER). Here we report that yeast and human Atg9 are lipid scramblases that translocate phospholipids between outer and inner leaflets of liposomes in vitro. Cryo-EM of fission yeast Atg9 reveals a homotrimer, with two connected pores forming a path between the two membrane leaflets: one pore, located at a protomer, opens laterally to the cytoplasmic leaflet; the other, at the trimer center, traverses the membrane vertically. Mutation of residues lining the pores impaired IM expansion and autophagy activity in yeast and abolished Atg9's ability to transport phospholipids between liposome leaflets. These results suggest that phospholipids delivered by Atg2 are translocated from the cytoplasmic to the luminal leaflet by Atg9, thereby driving autophagosomal membrane expansion. - Multifarious roles of lipid droplets in autophagy – Target, product, and what else?
Ogasawara Y; Tsuji T; Fujimoto T
Seminars in Cell & Developmental Biology, Elsevier BV, Mar. 2020, [Peer-reviewed]
Scientific journal - A method to selectively internalise submicrometer boron carbide particles into cancer cells using surface transferrin conjugation for developing a new boron neutron capture therapy agent
Tsuji T; Yoshitomi H; Ishikawa Y; Koshizaki N; Suzuki M; Usukura J
Journal of Experimental Nanoscience, 15, 1, 1, 11, 01 Jan. 2020, [Peer-reviewed], [Lead author, Corresponding author]
Scientific journal - ESCRT machinery mediates selective microautophagy of endoplasmic reticulum in yeast.
Schäfer JA; Schessner JP; Bircham PW; Tsuji T; Funaya C; Pajonk O; Schaeff K; Ruffini G; Papagiannidis D; Knop M; Fujimoto T; Schuck S
The EMBO journal, 39, 2, e102586, Dec. 2019, [Peer-reviewed]
Scientific journal - Predominant localization of phosphatidylserine at the cytoplasmic leaflet of the ER, and its TMEM16K-dependent redistribution.
Tsuji T; Cheng J; Tatematsu T; Ebata A; Kamikawa H; Fujita A; Gyobu S; Segawa K; Arai H; Taguchi T; Nagata S; Fujimoto T
PNAS, 116, 27, Jul. 2019, [Peer-reviewed], [Lead author]
English, Scientific journal - Definition of phosphoinositide distribution in the nanoscale.
Tsuji T*; Takatori S*(co-first author); Fujimoto T
Current Opinion in Cell Biology, 57, 33, 39, Apr. 2019, [Peer-reviewed], [Lead author]
Scientific journal - Lipids and lipid domains of the yeast vacuole.
Tsuji T; Fujimoto T
Biochemical Society transactions, 46, 5, 1047, 1054, Oct. 2018, [Peer-reviewed], [Lead author]
Scientific journal - Nuclear phosphatidylinositol 4,5-bisphosphate islets contribute to efficient RNA polymerase II-dependent transcription
Sobol M; Krausová A; Yildirim S; Kalasová I; Fáberová V; Vrkoslav V; Philimonenko V; Marášek P; Pastorek L; Čapek M; Lubovská Z; Uličná L; Tsuji T; Lísa M; Cvačka J; Fujimoto T; Hozak P
Journal of Cell Science, 131, 8, Company of Biologists Ltd, 15 Apr. 2018, [Peer-reviewed]
English, Scientific journal - Freeze-fracture-etching Electron Microscopy for Facile Analysis of Yeast Ultrastructure
Tsuji T; Fujimoto T
Bio-protocol, 7, 18, e2556, Sep. 2017, [Peer-reviewed], [Lead author]
English, Scientific journal - Niemann-Pick type C proteins promote microautophagy by expanding raft-like membrane domains in the yeast vacuole
Tsuji T; Fujimoto M; Tatematsu T; Cheng J; Orii M; Takatori S; Fujimoto T
ELIFE, 6, Jun. 2017, [Peer-reviewed], [Lead author]
English, Scientific journal - A New Electron Microscopic Method to Observe the Distribution of Phosphatidylinositol 3,4-bisphosphate
Aktar S; Takatori S; Tsuji T; Orii M; Ohsaki Y; Cheng J; Fujimoto T
ACTA HISTOCHEMICA ET CYTOCHEMICA, 50, 5, 141, 147, 2017, [Peer-reviewed]
English, Scientific journal - Structural Basis of the Inv Compartment and Ciliary Abnormalities in Inv/nphp2 Mutant Mice
Tsuji T; Matsuo K; Nakahari T; Marunaka Y; Yokoyama T
CYTOSKELETON, 73, 1, 45, 56, Jan. 2016, [Peer-reviewed], [Lead author]
English, Scientific journal - Spectroscopic and morphological studies on interaction between gold nanoparticle and liposome constructed with phosphatidylcholine
Tsukada C; Tsuji T; Matsuo K; Nomoto T; Kutluk G; Sawada M; Ogawa S; Yoshida T; Yagi S
INTERNATIONAL CONFERENCE ON SOLID FILMS AND SURFACES (ICSFS 2014), 76, 1, 012001, 2015, [Peer-reviewed]
English, International conference proceedings - Improving the systemic drug delivery efficacy of nanoparticles using a transferrin variant for targeting
Chiu Y. T. R; Tsuji T; Wang J. S; Wang J; Liu T. C; Kamei T. D
JOURNAL OF CONTROLLED RELEASE, 180, 33, 41, Apr. 2014, [Peer-reviewed]
English, Scientific journal - Study on interaction between phosphatidylcholine(PC) liposome and gold nanoparticles by TEM observation
Tsukada C; Tsuji T; Matsuo K; Nameki H; Yoshida T; Yagi S
Journal of Surface Analysis, 20, 3, 230, 233, 2014, [Peer-reviewed]
English, Scientific journal - Endocytic mechanism of transferrin-conjugated nanoparticles and the effects of their size and ligand number on the efficiency of drug delivery
Tsuji T; Yoshitomi H; Usukura J
MICROSCOPY, 62, 3, 341, 352, Jun. 2013, [Peer-reviewed], [Lead author]
English, Scientific journal - Assessment on a biological toxicity caused by single-walled carbon nanotubes
Takuma Tsuji; Jiro Usukura
Nano Biomedicine, 4, 2, 125, 132, 2012, [Peer-reviewed], [Lead author]
English, Scientific journal
- Distribution of Membrane Lipids Revealed by TEM
Takuma Tsuji, MEMBRANE, 47, 5, 281, 285, Sep. 2022, [Peer-reviewed], [Invited], [Lead author, Corresponding author]
The Membrane Society of Japan, Japanese - 小胞体膜のリン脂質分布制御機構と関連する疾患
辻琢磨; 藤本豊士, The Lipid, 32, 2, 126, 132, Oct. 2021, [Invited]
Japanese - オートファジーと脂肪滴の関わり
小笠原裕太; 辻琢磨; 藤本豊士, 医学のあゆみ 特集「オートファジー 分子機構・生物学的意義・疾患との関わり」, 272, 9, 789, 794, Feb. 2020, [Invited] - Definition of Phospholipid Distribution in Organelle Membranes
Takuma TSUJI; Toyoshi FUJIMOTO, Seibutsu Butsuri, 60, 3, 162, 164, 2020, [Invited]
Biophysical Society of Japan - リポクオリティの分析,可視化技術とその応用 2.膜リン脂質クオリティの可視化
辻琢磨; 藤本豊士, 実験医学, 36, 10, 1781‐1786, Jun. 2018, [Invited]
Japanese - Immunoelectron microscopy of gangliosides
Takuma Tsuji; Akikazu Fujita; Toyoshi Fujimoto, Methods in Molecular Biology, 1804, 231, 239, 2018, [Invited]
Humana Press Inc., English - 電子顕微鏡による脂肪滴と膜脂質の探索
藤本豊士; 大崎雄樹; 辻琢磨, Proceedings of Clinical Electron Microscopy, 35, 1‐3, 2016
Japanese
- 〔主要な業績〕ミクロオートファジーによる脂肪滴分解とその制御機構
辻琢磨
第96回日本生化学会大会, 02 Nov. 2023
31 Oct. 2023 - 02 Nov. 2023, [Invited] - 〔主要な業績〕ミクロオートファジーによる脂肪滴の分解
辻琢磨
第65回日本脂質生化学会, 02 Jun. 2023, Invited oral presentation
01 Jun. 2023 - 02 Jun. 2023, [Invited] - 〔主要な業績〕オルガネラ形態変化とミクロリポファジー
辻琢磨
第45回日本分子生物学会年会, 30 Nov. 2022
30 Nov. 2022 - 02 Dec. 2022, [Invited] - 〔Major achievements〕Molecular mechanism of micro-lipophagy in yeast
Tsuji T
72th Annual Meeting Korean Association of Anatomists, 19 Oct. 2022, English, Invited oral presentation
19 Oct. 2022 - 21 Oct. 2022, [Invited] - 〔主要な業績〕電子顕微鏡による膜脂質分布の解析
辻琢磨; 藤本豊士
日本膜学会第44年会, 09 Jun. 2022, Invited oral presentation
09 Jun. 2022 - 10 Jun. 2022, [Invited] - 〔主要な業績〕Molecular mechanism of micro-lipophagy in budding yeast
Tsuji T; Fujimoto T
日本顕微鏡学会第78回学術講演会, 12 May 2022, English, Nominated symposium
11 May 2022 - 13 May 2022 - 〔主要な業績〕出芽酵母におけるミクロリポファジー機構の解析
辻琢磨; 藤本豊士
第127回日本解剖学会総会全国学術集会, 27 Mar. 2022, Invited oral presentation
27 Mar. 2022 - 29 Mar. 2022, [Invited] - 〔Major achievements〕Distribution of vacuolar proteins in autophagy deficient yeasts
Tsuji T; Shibata R; Fujimoto T
第44回日本分子生物学会年会, 03 Dec. 2021, English, Nominated symposium
01 Dec. 2021 - 03 Dec. 2021, [Invited] - 〔主要な業績〕電子顕微鏡による膜脂質の解析
辻琢磨; 藤本豊士
第126回日本解剖学会総会・全国学術集会 第98回日本生理学会大会 合同大会, 29 Mar. 2021, Japanese, Invited oral presentation
28 Mar. 2021 - 30 Mar. 2021, [Invited] - 〔主要な業績〕膜脂質の対称性・非対称性分布
辻琢磨; 藤本豊士
日本顕微鏡学会 第45回関東支部講演会, 03 Mar. 2021, Japanese, Invited oral presentation
[Invited] - 〔主要な業績〕電子顕微鏡による膜脂質分子の可視化
辻琢磨
北海道大学 先端生命科学研究院 細胞装置学セミナー, 20 Nov. 2020, Japanese, Public discourse
[Invited] - 〔主要な業績〕電子顕微鏡による膜脂質局在解析
辻琢磨; 藤本豊士
第93回日本生化学会大会（web開催）, 15 Sep. 2020
14 Sep. 2020 - 16 Sep. 2020, [Invited] - 形質膜のホスファチジルセリンとカベオラ
辻琢磨; 藤本豊士
第125回日本解剖学会総会全国学術集会（誌上開催）, Mar. 2020, Poster presentation - Ca2+-dependent phosphatidylserine redistribution in the ER
Tsuji T; Cheng J; Tatematsu T; Ebata A; Kamikawa H; Taguchi T; Fujimoto T
60th International Conference on the Bioscience of Lipids, Jun. 2019, English, Poster presentation
[International presentation] - 〔主要な業績〕スクランブラーゼによる細胞内ホスファチジルセリン分布の変化
辻琢磨; 藤本豊士
第124回日本解剖学会総会全国学術集会, Mar. 2019, Japanese, Invited oral presentation
[Invited], [Domestic Conference] - 〔主要な業績〕電子顕微鏡によるホスファチジルセリンの細胞内分布解析
辻琢磨; 藤本豊士
第41回日本分子生物学会年会, Nov. 2018, Japanese, Invited oral presentation
[Invited], [Domestic Conference] - Subcellular distribution of phosphatidylserine revealed by freeze-fracture replica labeling electron microscopy
Tsuji T; Sumi E; Ebata A; Kamikawa H; Tatematsu T; Cheng J; Taguchi T; Fujimoto T
59th International Conference on the Bioscience of LIpids, Sep. 2018, English, Poster presentation
[International presentation] - 〔主要な業績〕電子顕微鏡による膜脂質分子の可視化
辻琢磨; 藤本豊士
第60回日本脂質生化学会, May 2018, Japanese, Invited oral presentation
[Invited], [Domestic Conference] - 〔主要な業績〕電顕による膜脂質ドメインの解析
辻琢磨; 藤本豊士
第123回日本解剖学会全国学術集会, Mar. 2018, Japanese, Invited oral presentation
[Invited], [Domestic Conference] - 〔主要な業績〕膜ミクロドメインとリポファジー
辻琢磨; 藤本萌; 立松律弥子; 程晶磊; 藤本豊士
第69回日本細胞生物学会, Jun. 2017, Japanese, Invited oral presentation
[Invited], [Domestic Conference] - ミクロオートファジーの分子機構
辻琢磨; 藤本萌; 立松律弥子; 程晶磊; 山木洸史; 藤本豊士
第122回日本解剖学会全国学術集会, Mar. 2017, Japanese, Poster presentation
[Domestic Conference] - Lipophagy: a Degradation Process of Lipid Droplets by Microautophagy in Budding Yeast
Tsuji T; Fujimoto M; Ebata A; Cheng J; Tatematsu T; Takatori S; Fujimoto T
12th International Congress of Cell Biology, Jul. 2016, English, Poster presentation
[International presentation] - 出芽酵母におけるホスファチジルセリンの細胞内分布
辻琢磨; 江畑葵; 上川裕輝; 立松律弥子; 程晶磊; 藤田秋一; 田口友彦; 藤本豊士
第68回日本細胞生物学会, Jun. 2016, Japanese, Poster presentation
[Domestic Conference] - リポファジー〜ミクロオートファジーによる脂肪滴分解〜
辻琢磨; 藤本萌; 高鳥翔; 藤本豊士
第121回日本解剖学会全国学術集会, Mar. 2016, Japanese, Poster presentation
[Domestic Conference] - 出芽酵母リポファジーにおける膜脂質動態に関する研究
辻琢磨; 高鳥翔; 藤本豊士
第６７回日本細胞生物学会大会, Jun. 2015, Japanese, Poster presentation
[Domestic Conference] - 出芽酵母lipophagyにおける膜動態
辻琢磨; 高鳥翔; 藤本豊士
第71回日本顕微鏡学会学術講演会, May 2015, Japanese, Poster presentation
[Domestic Conference] - 酵母リポファジーにおける膜動態
辻琢磨; 高鳥翔; 藤本豊士
第120回日本解剖学会全国学術集会, Mar. 2015, Japanese, Poster presentation
[Domestic Conference] - 一次繊毛微細構造と繊毛病の関係
辻琢磨; 横山尚彦
第119回日本解剖学会全国学術集会, Mar. 2014, Japanese, Poster presentation
[Domestic Conference] - トランスフェリン修飾粒子のがん細胞選択性の向上
辻琢磨; 吉富浩史; 臼倉治郎
第7回ナノバイオメディカル学会大会, Jan. 2013, Japanese, Oral presentation
[Domestic Conference] - Endocytic mechanism of transferrin-conjugated nanoparticles and the effects of their size and ligand number on the efficiency of drug delivery
Tsuji T; Yoshitomi H; Usukura J
The 10th International Nano Medicine and Drug Delivery (NanoDDS’12) Symposium, Dec. 2012, English, Poster presentation
[International presentation] - Targeted drug delivery using transferrin-conjugated submicron particles
Tsuji T; Yoshitomi H; Usukura J
2012 International Symposium on Micro-Nano Mechatronics and Human Science, Nov. 2012, English, Poster presentation
[International presentation] - トランスフェリン修飾粒子の径と細胞侵入機構、 薬物送達効率、がん細胞選択性の関係
辻琢磨; 吉富浩史; 臼倉治郎
第6回ナノバイオメディカル学会大会, Jul. 2012, Japanese, Oral presentation
[Domestic Conference] - トランスフェリン結合粒子の細胞内取り込み機構 と粒子サイズによる薬物送達効率の相違
辻琢磨; 吉富浩史; 臼倉治郎
第28回日本 DDS 学会学術集会, Jul. 2012, Japanese, Oral presentation
[Domestic Conference] - Endocytic mechanism on targeted drug delivery using transferrin-conjugated submicron particles
Tsuji T; Yoshitomi H; Usukura J
The 7th International Forum on Oxidative Stress and Aging, Nov. 2011, English, Oral presentation
[International presentation] - Investigation of cellular uptake mechanism of drug carrier nanoparticles for targeted drug delivery using transferrin
Tsuji T; Usukura J
The 3rd International Symposium on Surface and Interface of Biomaterials, Jul. 2011, English, Oral presentation
[International presentation] - Investigation of systemic drug delivery applications for a transferrin variant
辻琢磨; Chiu RYT; Kamei DT
第4回ナノバイオメディカル学会大会, Feb. 2011, Japanese, Oral presentation
[Domestic Conference] - A pilot study for the assessment on a biological toxicity caused by nano-particles
Tsuji T; Usukura J
10th International Symposium on Biomimetic Materials, Jan. 2010, English, Poster presentation
[International presentation] - 培養細胞を用いたイメージングによるナノリスクの評価法
辻琢磨; 臼倉治郎
第65回日本顕微鏡学会学術講演会, May 2009, Japanese, Oral presentation
[Domestic Conference] - A pilot study for the assessment on a biological toxicity caused by nano-particles
Tsuji T; Usukura J
9th International Symposium on Biomimetic Materials, Jan. 2009, English, Poster presentation
[International presentation]
■ Affiliated academic society
- THE JAPANESE SOCIETY OF MICROSCOPY
- JAPAN SOCIETY FOR CELL BIOLOGY
- THE JAPANESE ASSOCIATION OF ANATOMISTS
- 日本脂質生化学会
- 出芽酵母液胞膜におけるホスファチジルセリン非対称性分布のメカニズム
2024年度地神芳文記念研究助成金
Sep. 2024 - Aug. 2025
辻 琢磨
特定非営利活動法人 酵母細胞研究会, 北海道大学, Principal investigator - Elucidation of nuclear lipid droplet functions
Grants-in-Aid for Scientific Research
01 Apr. 2022 - 31 Mar. 2025
藤本 豊士; 大崎 雄樹; 辻 琢磨
A. 核内脂肪滴がPML小体に及ぼす影響の解析：アミノ酸飢餓状態においた細胞ではオートファジー依存性に多数の核内脂肪滴が形成され、PML小体と共局在することがわかった。前年度に確立したmClover-PMLノックイン細胞を用いた蛍光褪色回復法 (FRAP) による解析により、アミノ酸飢餓条件では核内脂肪滴の形成に伴ってmClover-PMLの蛍光回復が遅延し、PML小体の液滴としての性質が変化していることが明らかになった。
B. 細胞質脂肪滴と核内脂肪滴の相関関係の解析：TG分解酵素 (ATGL)をノックアウトした細胞をアミノ酸飢餓条件で培養すると、野生株以上に細胞質脂肪滴は増加するが、核内脂肪滴の形成はほとんど見られず、ATGLを再導入するとこの表現型は消失した。野生株細胞をATGL阻害剤処理下にアミノ酸飢餓においても細胞質脂肪滴の増加と核内脂肪滴の形成不全が見られた。その後にATGL阻害を解除すると核内脂肪滴が出現し、核内膜のジアシルグリセロール (DAG) が増加した。このようなATGL阻害・回復と核内膜DAGの減少・増加の相関は通常培養条件でも見られた。またトリアシルグリセロール (TAG) 合成酵素 (DGAT1, DGAT2) 阻害も核内膜DAGを増加させた。これらの結果から細胞質脂肪滴の分解で生じたDAGが核内膜に流入して、TAG合成、核内脂肪滴形成をもたらすと考えられた。
C. PML小体とDAGの解析：核内のDAGは核内膜以外にPML小体にも認められた。PML小体のDAGは４つの主要な脂質エステル合成酵素を欠損し、脂肪滴がほぼ存在しない細胞においても見られた。この結果はPML小体の内部に脂肪滴とは別の脂質性の構造があることを示唆した。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Juntendo University, 22H00446 - a
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Apr. 2022 - Mar. 2025
辻 琢磨
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Juntendo University, Principal investigator, 22K06818 - 多階層高次構造体群が駆動するオートファジーダイナミクス
戦略的な研究開発の推進 戦略的創造研究推進事業 CREST
2020 - 2025
野田 展生
オートファジーは細胞が自身の一部を分解して再利用する基本的な生命現象の一つで、我々が健康に生きていくために必須の役割を担っています。オートファジーが起きる過程では細胞内で脂質膜の複雑な再編成が行われ、それは多階層の高次構造体群が担っていますが、その仕組みはよくわかっていません。本研究では、オートファジーの諸過程を必要最小限の因子を用いて試験管内で再現し、単純化することでメカニズムの本質に迫ります。
科学技術振興機構, 公益財団法人微生物化学研究会 - a
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
Apr. 2022 - Mar. 2024
辻 琢磨
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Juntendo University, Principal investigator, 22H04654 - ミクロリポファジーの脂肪滴・液胞膜接着機構と生理的意義の研究
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
Apr. 2020 - Mar. 2022
辻 琢磨
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Juntendo University, 20H05339 - カルシウム依存性に起こる細胞内ホスファチジルセリンの分布変化
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Apr. 2019 - Mar. 2022
辻 琢磨
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Juntendo University, 19K07265 - Studies on the function of the lipid droplet surface
Grants-in-Aid for Scientific Research
01 Apr. 2018 - 31 Mar. 2021
Fujimoto Toyoshi
The surface of lipid droplets (LDs) has properties different from other biological membranes and recruit unique proteins. In hepatocytes exposed to the endoplasmic reticulum stress, we discovered that lipids, which are normally secreted as lipoproteins, enter the nucleus and generate nuclear LDs. These nuclear LDs recruit and activate CCTα, an isoform of the enzyme critical for phosphatidylcholine synthesis, thereby contributing to mitigation of the endoplasmic reticulum stress. In cells under starvation, free fatty acids derived from digested self materials generate cytoplasmic LDs. On those LDs, CCTβ3, a different isoform of CCT, is activated, and this helps cells to maintain autophagy and survive for a prolonged time in starvation.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), 18H04023 - Membrane domain and lipophagy
Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
Apr. 2017 - Mar. 2019
Tsuji Takuma; FUJIMOTO TOYOSHI; CHENG JINGLEI; TATEMATSU TSUYAKO
In budding yeast in the stationary phase, the vacuole forms sterol-rich raft-like membrane domains and degrades lipid droplets (LDs) in its lumen (lipophagy). To reveal the relationship between the domain formation and lipophagy, we examined the membrane dynamics in the lipophagic process by using the quick-freezing and freeze-fracture replica electron microscopy. We found that LDs are engulfed by invagination of raft-like domains toward the vacuolar lumen.
Sterol needs to be supplied to the vacuolar membrane for the raft-like domain formation. In yeast lacking Ncr1 and Npc2, sterol accumulated in the vacuolar lumen, formation of raft-like domains was significantly reduced, and lipophagy was suppressed. We also found that Ncr1 and Npc2 are essential for formation of the vacuolar membrane domains in acute nitrogen starvation, and that sterol is derived from the intralumenal vesicles of MVB.
Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Nagoya University, 17K15544 - Cell biological studies on membrane lipid distribution and dynamics
Grants-in-Aid for Scientific Research
01 Apr. 2015 - 31 Mar. 2018
Fujimoto Toyoshi; YAMAMOTO HAYASHI; TAGUCHI TOMOHIKO; TAKATORI SHO
Electron microscopic methods to label phosphatidylinositol 3,5-bisphosphate, phosphatidylinositol 3,4-bisphosphate, and phosphatidylserine by quick-freezing and freeze-fracture replica labeling were established and distribution of respective phospholipids were defined at the nanometer scale. Involvement of PML-II in formation of nuclear lipid droplets was found and close relationship between nuclear lipid droplets and PML nuclear body as well as nucleoplasmic reticulum, which is an extension of the nuclear envelope, was shown. Microautophagy of lipid droplets that occurs in budding yeast at stationary phase and in acute nitrogen starvation was shown to proceed in a raft-like membrane domain of the vacuole membrane and Niemann-Pick type C proteins were found to play a critical role in transportation of sterol to generate the membrane domain.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Nagoya University, 15H02500 - Development of a new freeze replica method to observe the hydrophobic portion of membrane lipids
Grants-in-Aid for Scientific Research
01 Apr. 2015 - 31 Mar. 2017
Fujimoto Toyoshi; MAKOTO ARITA
Phospholipids constitute the basic framework of biological membranes and they are known to contain highly variable acyl chains in their hydrophobic tail portion. However, it is hardly known how those acyl chains distribute in the cellular membrane. In this project, we developed a method to define the nano-scale distribution of a specific kind of acyl chain by utilizing alkyne-labeled fatty acids and quick-freezing freeze-fracture electron microscopy. By performing click reaction on the freeze-fracture replica, labeling for the acyl chain was observed in cellular membranes, and moreover, it was shown to form clusteres in a limited region of the membrane.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Nagoya University, 15K14506 - Investigation of intracellular distribution and physiological importance of phosphatidylserine
Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
Apr. 2015 - Mar. 2017
Tsuji Takuma
Phosphatidylserine (PS) is one of phospholipids and is a component of the cell membrane. The physiological importance of PS is not well understood because of methodological difficulty to define PS distribution, although asymmetrical or heterogeneous distribution of PS would have essential function in the cell. In this study, we investigated PS distribution by utilizing quick-freeze and freeze-fracture replica labeling electron microscopy. As a result, we found that PS distributed evenly on the both leaflet of the ER and nuclear membrane and unevenly on the golgi membrane of budding yeast. Furthermore PS is labeled on the extracellular leaflet of plasma membrane and cytosolic leaflet of ER/outer nuclear membrane of MEF cell.
Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Nagoya University, 15K18954
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