Molecular mechanism for synapse-nanocolumn formation and synapse disorders
| Project/Area Number |
17H03678
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | National Institute for Physiological Sciences |
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Principal Investigator |
Fukata Masaki 生理学研究所, 分子細胞生理研究領域, 教授 (00335027)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | シナプス / 蛋白質 / 脂質 / 脳・神経 / 酵素 / 生理学 / ナノドメイン / ナノカラム / タンパク質 |
|---|
| Outline of Final Research Achievements |
Regulated trans-synaptic communication plays a pivotal role in synaptic transmission. Although recent studies have identified a large number of synaptic adhesion molecules, the molecular mechanism for trans-synaptic communication remains incompletely understood. In this study, we showed the crystal structure of human LGI1-ADAM22 complex, revealing a 2:2 heterotetrameric assembly through the intermolecular LGI1-LGI1 interaction. A pathogenic R474Q mutation of LGI1 is located in the LGI1-LGI1 interface and disrupts the higher-order assembly of the LGI1-ADAM22 complex in vitro and in a mouse model for familial epilepsy. These studies support the notion that the LGI1-ADAM22 complex functions as the trans-synaptic machinery for precise synaptic transmission and disruption of this linkage causes the epileptic disorder.
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| Academic Significance and Societal Importance of the Research Achievements |
てんかんの原因となる分泌蛋白質LGI1と、その受容体であるADAM22が結合した状態の立体構造を決定することで、ADAM22がLGI1を介して神経細胞間の橋渡しをする様子を明らかにした。また、これまでに知られていたLGI1変異の中で発症の仕組みが不明であった変異に関して、新たな発症の仕組みを明らかにした。本研究は、神経シナプス機能の調節機構とてんかん病態の一端を明らかにしたと言える。
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Report
(4 results)
Research Products
(44 results)
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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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[Journal Article] Structural basis of epilepsy-related ligand-receptor complex LGI1-ADAM222018
Author(s)
Yamagata A, Miyazaki Y, Yokoi N, Shigematsu H, Sato Y, Goto-Ito S, Maeda A, Goto T, Sanbo M, Hirabayashi M, Shirouzu M, Fukata Y, Fukata M, Fukai S
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Journal Title
Related Report
Peer Reviewed / Open Access
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[Journal Article] Secreted Metalloproteinase ADAMTS-3 Inactivates Reelin2017
Author(s)
Ogino H, Hisanaga A, Kohno T, Kondo Y, Okumura K, Kamei T, Sato T, Asahara H, Tsuiji H, Fukata M, Hattori M
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Journal Title
J Neurosci
Volume: 37
Issue: 12
Pages: 3181-3191
DOI
Related Report
Peer Reviewed / Open Access
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