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KAKEN_18K06490seika.pdf
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Download
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:84.2 KB
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:May 17, 2022 |
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Total downloads since May 17, 2022 : 167
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GABAA受容体新規結合因子GARLHを介した抑制性シナプスの新しい制御機構
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GABAA ジュヨウタイ シンキ ケツゴウ インシ GARLH オ カイシタ ヨクセイセイ シナプス ノ アタラシイ セイギョ キコウ
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GABAA juyōtai shinki ketsugō inshi GARLH o kaishita yokuseisei shinapusu no atarashii seigyo kikō
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Novel molecular mechanisms to regulate inhibitory synapse functions through GABAA receptor regulatory Lhfpl (GARLH)
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山崎, 世和
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ヤマサキ, トキワ
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Yamasaki, Tokiwa
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慶應義塾大学・医学部 (信濃町) ・助教
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Research team head
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科研費研究者番号 : 60581402
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2021
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科学研究費補助金研究成果報告書
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2020
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本研究では、申請者が世界で初めて発見したGABAA受容体新規結合因子GARLHに焦点を当て、抑制性シナプスを制御する新たな分子機構を明らかにすることを目的として研究を遂行した。その結果、GARLHが、抑制性接着因子NL2だけでなく、興奮性接着因子NL1とも結合し、NL1を抑制性シナプスへ局在化することを明らかにした。加えて、GARLHと結合することが明らかになったNL1について、HAノックインマウスを用いたプロテオーム解析を行い、NL1の結合分子を網羅的に同定した。また、近接依存性ビオチン化標識酵素とGARLHの融合タンパク質をマウスの脳に発現させ、未知の結合因子を探索する系を立ち上げた。
Previously we identified GARLH as a novel GABAA receptor binding protein. In this study, we investigated the molecular mechanisms which regulate inhibitory synapses through GARLH. We found that GARLH binds not only inhibitory adhesion NL2, but also excitatory adhesion NL1, and that GARLH localizes NL1 from excitatory to inhibitory synapses. Additionally, we performed proteome analysis of NL1 using HA-NL1 knock-in mice and revealed NL1-interacting proteins. We also designed fusion proteins of GARLH and proximity labeling enzyme, TurboID, and expressed in mouse brain. We are now investigating to identify novel GARLH binding proteins using this GARLH-TurboID system.
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研究種目 : 基盤研究 (C) (一般)
研究期間 : 2018～2020
課題番号 : 18K06490
研究分野 : 神経シナプス科学
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