Proteomic analysis with high spatiotemporal resolution at the synapse
Project/Area Number |
19K22439
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
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Research Institution | National Institute for Physiological Sciences |
Principal Investigator |
Fukata Yuko 生理学研究所, 分子細胞生理研究領域, 准教授 (40416186)
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Project Period (FY) |
2019-06-28 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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Keywords | プロテオミクス / シナプス / タンパク質相互作用 / 界面活性剤 / タンパク質分解 / 酵素-基質 |
Outline of Research at the Start |
生体蛋白質は時々刻々と多様な分子群と相互作用することにより、成熟、輸送を経て適所に局在化することで、生理機能を発揮する。これらいずれの過程が障害されても蛋白質はその機能を果たせず、時には疾患の要因となる。本研究では、超解像プロテオミクス法の開発に挑戦する。これまで見過されてきた蛋白質相互作用を明らかにして、シナプス制御機構やシナプス病態機構の理解につながる成果を得ることを目指す。
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Outline of Final Research Achievements |
Biological proteins do not function alone, but interact with a variety of proteins to perform their physiological functions. Disruption of these protein-protein interactions could cause dysfunction of the protein, sometimes causing diseases. Therefore, identifying the true protein-protein interactions with high spatiotemporal resolution is extremely important. In this study, we selected the epilepsy-related proteins, ADAM22 and LGI1, and the enzymes that regulate protein localization as model proteins. We succeeded to identify novel protein-protein interactions which occur in the insoluble synaptic fraction and transiently occur in cells.
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Academic Significance and Societal Importance of the Research Achievements |
シナプス不溶性画分からタンパク質複合体を可溶化、精製可能な実験条件(界面活性剤の種類と濃度)を確立し、脳シナプス膜画分におけるてんかん関連タンパク質ADAM22を含む複合体を網羅的、特異的に同定することに成功した。また、リン酸化修飾に関連した一過的なタンパク質相互作用を明らかにすることに成功した。このように、新たなタンパク質複合体の精製技術を開発することにより、これまで見過されてきたタンパク質相互作用を明らかにして、シナプス制御機構やてんかん病態の理解につながる成果を得た。
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Report
(4 results)
Research Products
(45 results)
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[Journal Article] 14-3-3 proteins stabilize LGI1-ADAM22 levels to regulate seizure thresholds in mice2021
Author(s)
Norihiko Yokoi, Yuko Fukata, Kei Okatsu, Atsushi Yamagata, Yan Liu , Makoto Sanbo, Yuri Miyazaki, Teppei Goto, Manabu Abe , Hidetoshi Kassai, Kenji Sakimura, Dies Meijer, Masumi Hirabayashi, Shuya Fukai, Masaki Fukata
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Journal Title
Cell Reports
Volume: 37
Issue: 11
Pages: 110107-110107
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Acyl-PEGyl exchange gel-shift (APEGS) assay for palmitoylation quantification2021
Author(s)
van der Knoop M Marieke M*、Maroofian Reza*、Fukata Yuko*、van Ierland Yvette、Karimiani G Ehsan、Lehesjoki Anna-Elina、Muona Mikko、Paetau Anders、Miyazaki Yuri、Hirano Yoko、Selim Laila、-----32名-----、Striano Pasquale、Severino Mariasavina、Fukata Masaki#、Hilhorst-Hofstee Yvonne#、Houlden Henry#
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Journal Title
Electrophoresis Letters
Volume: 65
Issue: 2
Pages: 41-45
DOI
NAID
ISSN
2189-2628, 2189-2636
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Canonical versus non-canonical transsynaptic signaling of neuroligin 3 tunes development of sociality in mice2021
Author(s)
Yoshida T, Yamagata A, Imai A, Kim J, Izumi H, Nakashima S, Shiroshima T, Maeda A, Iwasawa-Okamoto S, Azechi K, Osaka F, Saitoh T, Maenaka K, Shimada T, Fukata Y, Fukata M, Matsumoto J, Nishijo H, Takao K, Tanaka S, Okabe S, Tabuchi K, Uemura T, Mishina M, Mori H & Fukai S
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Journal Title
Nature Communications
Volume: 12(1)
Issue: 1
Pages: 1848-1848
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Targeting CCR5 trafficking to inhibit HIV-1 infection2019
Author(s)
Boncompain Gaelle、Herit Floriane、Tessier Sarah、Lescure Aurianne、Del Nery Elaine、Gestraud Pierre、Staropoli Isabelle、Fukata Yuko、Fukata Masaki、Brelot Anne、Niedergang Florence、Perez Franck
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Journal Title
Science Advances
Volume: 5
Issue: 10
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Limbic Encephalitis in a Cat with Hippocampal Necrosis, putatively associated with DCC (deleted in colorectal cancer; Netrin-1 Receptor) Antibodies2019
Author(s)
Hasegawa D, Ohnishi Y, Koyama E, Matsunaga S, Ohtani S, Nakanishi A, Shiga T, Chambers JK, Uchida K, Yokoi N, Fukata Y, Fukata M.
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Journal Title
J Vet Intern Med
Volume: 印刷中
Issue: 3
Pages: 1440-1445
DOI
Related Report
Peer Reviewed
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