Structural basis of splicing-dependent regulation for synaptogenesis
| Project/Area Number |
16H04749
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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 |
Structural biochemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Research Collaborator |
Maeda Asami
Shiroshima Tomoko
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
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| Keywords | シナプス / 結晶構造解析 / 選択的スプライシング / タンパク質複合体 / 蛋白質複合体 / 蛋白質 / 構造生物学 / X線結晶解析 / シナプスオーガナイザー |
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| Outline of Final Research Achievements |
We performed X-ray crystallographic, quantitative interaction , and synaptogenic analyses for LRRTM-Neurexin complex and SALM-PTPδ complexes, those are cell-adhesion complexes capable of regulating synaptogenesis. As a result, we elucidated the mechanism how alternative splicing can regulate the interaction of these complexes. In addition, we revealed the mechanism for selective binding of neurexin to LRRTM1 and LRRTM2 among four LRRTM members in human. Moreover, we found the novel synaptogenic mechanism by SALM-PTPδ complex, in which the dimerization of SALM is crucial for synaptogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
脳は数千億の神経細胞が複雑な回路を形成して成り立っている。神経細胞同士はシナプスを介して連結しており、シナプス形成の異常や破綻は自閉症や統合失調症など精神発達障害の原因となる。シナプスの形成はシナプスオーガナイザーと呼ばれる細胞接着因子の複合体形成が必須である。本研究はシナプス形成を司るシナプスオーガナイザー複合体の形成と制御の機構を、立体構造とそれに基づく詳細な解析によって明らかにしたものである。これらのシナプスオーガナイザーの遺伝子異常が精神発達障害の原因となることも知られており、本研究は精神発達障害の機構の解明や、それに対する薬剤開発につながるような重要な基礎研究と言える。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Structural insights into ubiquitin phosphorylation by PINK12018
Author(s)
Okatsu Kei、Sato Yusuke、Yamano Koji、Matsuda Noriyuki、Negishi Lumi、Takahashi Akiko、Yamagata Atsushi、Goto-Ito Sakurako、Mishima Masaki、Ito Yutaka、Oka Toshihiko、Tanaka Keiji、Fukai Shuya
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Journal Title
Scientific Reports
Volume: 8
Issue: 1
Pages: 10382-10382
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Distinct Roles for the N- and C-terminal Regions of M-Sec in Plasma Membrane Deformation during Tunneling Nanotube Formation.2016
Author(s)
Kimura S, Yamashita M, Yamakami-Kimura M, Sato Y, Yamagata A, Kobashigawa Y, Inagaki F, Amada T, Hase K, Iwanaga T, Ohno H, Fukai S.
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Journal Title
Scientific Reports
Volume: 6
Issue: 1
Pages: 33548-33548
DOI
NAID
Related Report
Peer Reviewed / Open Access
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