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興奮性シナプスにおける、基盤構造の生成:SynGAP凝集体はPSD95を介して受容体を選択的に保持する
https://doi.org/10.15102/1394.00002546
https://doi.org/10.15102/1394.00002546ee681cf8-8cc6-481e-9255-828d191c0928
名前 / ファイル | ライセンス | アクション |
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Acharya-FullText (3.3 MB)
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Acharya-FinalExamAbstract (43.0 kB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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公開日 | 2022-10-12 | |||||||
タイトル | ||||||||
言語 | ja | |||||||
タイトル | 興奮性シナプスにおける、基盤構造の生成:SynGAP凝集体はPSD95を介して受容体を選択的に保持する | |||||||
タイトル | ||||||||
言語 | en | |||||||
タイトル | SynGAP Condensates Recruit PSD95, and Selectively Retain Multivalent Receptors, Functioning as the Basic Platform for Generating Neuronal Excitatory Synapses | |||||||
言語 | ||||||||
言語 | eng | |||||||
資源タイプ | ||||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||
資源タイプ | doctoral thesis | |||||||
ID登録 | ||||||||
ID登録 | 10.15102/1394.00002546 | |||||||
ID登録タイプ | JaLC | |||||||
アクセス権 | ||||||||
アクセス権 | open access | |||||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||
著者 (英) |
Acharya, Saahil
× Acharya, Saahil
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抄録 | ||||||||
内容記述タイプ | Other | |||||||
内容記述 | The post-synaptic structure consists of nano-scale domains that need to be precisely apposed to pre-synaptic neurotransmitter release sites. This exquisite assembly of post-synaptic receptors and scaffold proteins is essential for proper synaptic function. However, the biophysical mechanisms that retain receptors and scaffold proteins at the post-synapse are not well understood. Specifically, a mechanism that can induce clusters of PSD95, a key scaffold protein, at low concentrations, such as those expected before the formation of functional post-synapses, and which can induce long-term retention of post-synaptic receptors, remains to be postulated. In this thesis, I show that SynGAP forms phase-separated condensates through homophilic interactions mediated by its C-terminal coiled-coil domain as well as its intrinsically disordered region. SynGAP recruits PSD95 into these condensates, and this allows recruitment and immobilization of receptors such as Neuroligin and AMPA receptors (via TARPs), which have PDZ binding sites. I also found that oligomerization of Neuroligin and AMPA receptors anchors these receptors in SynGAP condensates. Functional oligomeric Neuroligin and AMPA receptors (GluA1 subunits linked to TARP ɤ2) are immobilized for longer durations as they diffuse through phase-separated condensates containing PSD95, compared to monomeric Neuroligin and TARP ɤ2. Together, these discoveries reveal how liquid-like assemblies of SynGAP can recruit PSD95 molecules, and retain trans-membrane receptors like Neuroligin and AMPA receptors depending on their oligomerization state. | |||||||
口頭試問日 | ||||||||
2022-08-23 | ||||||||
学位授与年月日 | ||||||||
学位授与年月日 | 2022-09-30 | |||||||
学位名 | ||||||||
学位名 | Doctor of Philosophy | |||||||
学位授与番号 | ||||||||
学位授与番号 | 甲第101号 | |||||||
学位授与機関 | ||||||||
学位授与機関識別子Scheme | kakenhi | |||||||
学位授与機関識別子 | 38005 | |||||||
学位授与機関名 | Okinawa Institute of Science and Technology Graduate University | |||||||
著者版フラグ | ||||||||
出版タイプ | VoR | |||||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||
権利 | ||||||||
権利情報 | © 2022 The Author |