嗅覚受容体のフィードバックを誘発するために展開されたタンパク質の応答をコオプティングします
Ryan P Dalton1, David B Lyons, Stavros Lomvardas
1Department of Anatomy, University of California San Francisco, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California San Francisco, San Francisco, CA 94158, USA.
Cell
|October 15, 2013
まとめ
嗅覚受容体 (OR) タンパク質は,神経のアイデンティティを維持するために,展開されたタンパク質応答 (UPR) を誘発します. このプロセスは,ATF5の選択的翻訳を含み,Adcy3発現と永久的なOR選択につながります.
科学分野:
- 神経科学は神経科学である.
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- 嗅覚センサーニューロン (OSN) の嗅覚受容体 (OR) 発現は,数千のORアレルのうちの1つを選択することを意味します.
- この特定のOR転写選択の保存にフィードバックメカニズムが不可欠です.
- OSNがORを検出し,この選択を核にシグナルする正確な方法はよく理解されていません.
研究 の 目的:
- ORタンパク質が核にフィードバック信号を生成するメカニズムを解明する.
- OR発現とニューロンアイデンティティの維持における展開タンパク質応答 (UPR) の役割を調査する.
主な方法:
- OR発現における展開タンパク質応答 (UPR) の役割を調査した.
- OSNにおけるPerk, eif2α, ATF5,およびAdcy3を含むシグナル伝達経路を調べました.
- ORフィードバックシグナリングの2段階モデルを提案し,サポートしました.
主要な成果:
- ORタンパク質はUPRを活性化させ,perk媒介によるeif2αのリン酸化を誘導する.
- これにより,活性化転写因子5 (ATF5) の選択的翻訳が起こります.
- ATF5はAdcy3トランスクリプションを駆動し,その後,UPRを緩和し,OR発現を安定させます.
結論:
- UPRは,ニューロンのアイデンティティと細胞の運命へのコミットメントにおいて重要な役割を果たします.
- 2段階のフィードバックモデルは,OR発現がどのように維持されるかを説明します:最初のUPR活性化に続いてAdcy3介のストレス緩和.
- このメカニズムは,選択された OR アレルのOSNの永続性を保証します.
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