| Project/Area Number |
15H04279
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | National Institute for Physiological Sciences |
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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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| Research Collaborator |
YOKOI Norihiko 生理学研究所, 分子細胞生理研究領域, 助教 (50710969)
HIRATA Tetsuya 生理学研究所, 分子細胞生理研究領域, 特任助教 (90780651)
TAKAHASHI Naoki
INAHASHI Hiroki
SEKIYA Atsushi
MURAKAMI Tatsuro
FURUKAWA Sachiko
SUZUKI Yumi
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2017: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2016: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2015: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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| Keywords | シナプス / AMPA受容体 / グルタミン酸受容体 / パルミトイル化脂質修飾 / PSD-95 / てんかん / 脱パルミトイル化 / ナノドメイン / 脱パルミトイル化酵素 / パルミトイル化 / LGI1 / 神経科学 / 脳神経疾患 / 生理学 / 蛋白質 / 遺伝学 / 超解像顕微鏡 / NMDA受容体 |
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| Outline of Final Research Achievements |
AMPA-type glutamate receptor (AMPAR) mediates most of fast synaptic transmission in the brain. Although AMPAR dynamically enters and exits the postsynaptic membrane in a synaptic activity-dependent manner, the underlying molecular mechanism is still incompletely understood. In this study, we focused on palmitoylation and protein-protein interactions of PSD-95, an essential scaffolding protein for AMPAR. We discovered a novel enzyme, ABHD17, which catalyzes PSD-95 depalmitoylation and thereby plays an important role in the (re)organization of the postsynaptic platform for AMPAR anchoring. We also found that the epilepsy-related ligand/receptor complex of LGI1 and ADAM22 regulates AMPAR functions through the direct interaction with PSD-95. Furthermore, we revealed the structural basis of the LGI1-ADAM22 protein complex at the synapse and its patho-physiological role in epileptogenesis.
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