2018 Fiscal Year Final Research Report
Elucidating the synaptic pathology of neurodevelopmental disorders-Comprehensive and quantitative analysis of signaling pathway abnormalities
| Project/Area Number |
16K15554
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Psychiatric science
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| Research Institution | Niigata University |
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Principal Investigator |
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| Research Collaborator |
Igarashi Michihiro
Egawa Jun
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 統合失調症 / 自閉症 / リン酸化プロテオミクス / GAP43 / NLGN3 |
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| Outline of Final Research Achievements |
We selected GAP43 and NLGN3, which are risk genes for schizophrenia and autism, among genes whose phosphorylation sites are important for neurodevelopment identified by phosphoproteomics of growth cones, and performed functional analysis. The GAP43 D23G mutation identified in an autism patient was introduced into Hela cells and observed immunohistologically. The results revealed that D23G-transduced cells showed less nuclear expression of GAP43 than wild-type transfected cells. Furthermore, the distribution of the phosphorylation site (S745) of NLGN3 was subjected to immunoblotting using synaptosomes, and immunohistological observation using primary culture neurons. These findings suggest that phosphorylation may be functional at both the axonal tip and the synapse.
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| Free Research Field |
発達精神医学
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| Academic Significance and Societal Importance of the Research Achievements |
統合失調症や自閉症の妥当性の高いリスク遺伝子は全エクソーム解析などの網羅的な解析法によって同定された。本研究ではタンパクレベルの網羅的解析であるリン酸化プロテオミクスで同定された神経発達に重要と考えられるリン酸化部位のうち統合失調および自閉症のリスク遺伝子に存在するものを選定してそれらの機能についての知見を得ることができた。タンパクレベルの妥当性の高い知見を蓄積することにより、さらに高次レベルの知見を得るための確かな土台となる。このように各レベルで妥当性の高い土台を重ねていくことにより、それらの疾患の病態解明および治療法開発に結び付くと考えられる。。
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