Analysis of the centrosome function via CAMDI and higher brain function during stress in CAMDI knockout mice
| Project/Area Number |
17K08793
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | CAMDI / 記憶 / 学習 / KIBRA / 中心体 / 移動 / dilation / 自閉症 / AMPA / ストレス / PTSD / AMPA受容体 / 記憶・学習 / ドラッグリポジショニング |
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| Outline of Final Research Achievements |
KIBRA was identified as a novel CAMDI-binding protein that retains AMPAR in the cytosol after internalization. KIBRA inhibited CAMDI-dependent Rab11 activation, thereby attenuating AMPAR cell surface expression. Knockdown of CAMDI in hippocampal neurons increased the amount of internalized alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR) and attenuated the chemical long-term potentiation (LTP)-dependent cell surface expression of AMPAR. CAMDI-deficient mice exhibited impaired recognition memory and spatial reference memory.
In migrating cortical neurons, CAMDI was localized at a structure, called dilation, with the centrosome. In dilation, it became clear that the oscillation of EGFP-CAMDI stable-unstable states was repeatedly during cortical migration.
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| Academic Significance and Societal Importance of the Research Achievements |
自閉症などの発達障害は、幼児期や学童期はもちろん、「大人の発達障害」と呼ばれるように、日常生活に大きな支障をきたし社会的な問題となっている。しかしその根本的な発症要因は未だ解明されていない。そのため、治療や対処法に関しても統一的な解釈がなく、患者数、治療費などによる社会的な損失は計り知れない。
大脳皮質発生過程はマウスとヒトにおいて共通する分子メカニズムがあると考えられている。本研究は自閉症を含む精神疾患の病理と分子メカニズムの解明、将来的には精神疾患の予防、治療へとつながると考えており、その基礎研究として貢献できると考えている。
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Report
(4 results)
Research Products
(9 results)
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[Journal Article] Critical role of CRAG, a splicing variant of centaurin-γ3/AGAP3, in ELK1-dependent SRF activation at PML bodies.2019
Author(s)
Nagashima S, Takeda K, Shiiba I, Higashi M, Fukuda T, Tokuyama T, Matsushita N, Nagano S, Araki T, Kaneko M, Shioi G, Inatome R, Yanagi S.
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Journal Title
Sci Rep
Volume: 9
Issue: 1
Pages: 20107-20107
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] MITOL prevemts ER stress-induced apoptosis by IRE1 ubiquitylation at mitochondrial-ER contact sites.2019
Author(s)
Takeda, K., Nagashima, S., Shiiba, I., Uda, A., Tokuyama, T., Ito, N., Fukuda, T., Matsushita, N., Ishido, S., Iwawaki, T., Uehara, T., Inatome, R., and Yanagi, S.
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Journal Title
EMBO J.
Volume: 38
Issue: 15
DOI
Related Report
Peer Reviewed / Open Access
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