NMDA受容体信号のシナプスまたはエクストラシナプス起源をコードし,核に変換する
Anna Karpova1, Marina Mikhaylova, Sujoy Bera
1RG Neuroplasticity, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany.
Cell
|March 5, 2013
まとめ
Jacobタンパク質は,シナプスおよびエクストラシナプスN-メチル-D-アスパルテート受容体 (NMDAR) 信号を区別するメッセンジャーとして作用します. その核輸送とリン酸化状態は,神経細胞の生存または死亡を決定し,シナプス可塑性に影響します.
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.
- 細胞シグナル伝達 細胞信号伝達
背景:
- N-メチル-D-アスパラテート受容体 (NMDARs) は2つの役割を持っています:シナプス活性化は生存と可塑性を促進し,エクストラシナプス活性化は神経変性を引き起こす.
- 核がこれらの対立するNMDAR信号を区別し,それに反応するメカニズムは,ほとんど不明のままである.
研究 の 目的:
- 核へのシナプスおよびエクストラシナプスNMDAR信号の変換と差別を担当するタンパク質メッセンジャーを特定する.
- これらのNMDAR媒介経路の核輸送とシグナル伝達を制御する分子機構を解明する.
主な方法:
- NMDAR信号伝達におけるJacobタンパク質の役割を調査した.
- ERK1/2.2によるセリン-180におけるヤコブリン酸化を分析するために生化学的分析を用いた.
- ERKの活動に対するジェイコブ・トラフィックの依存性と,α-インターネクシンとの相互作用を調査した.
- 細胞生存とシナプス可塑性に対するジェイコブスの核リン酸化状態の影響を評価した.
主要な成果:
- ジェイコブタンパク質は,シナプス対エクストラシナプスNMDAR信号のメッセンジャーとして作用します.
- シナプス的なNMDARの活性化は,エクストラシナプスではないが,ERK1/2.2.経由でセリン-180でのヤコブリン酸化を誘導する.
- ERKの活動は,シナプスサイトから長距離のヤコブ取引に不可欠です.
- α-インターネクシンとの結合は,核通過中にジェイコブ/ERK複合体の脱酸化を防ぐ.
- Jacobの核リン酸化状態は,細胞死または生存およびシナプス可塑性におけるその役割を決定する.
結論:
- ジェイコブは,有益なNMDAR信号と有害なNMDAR信号を区別する核標的メッセンジャーです.
- ジェイコブのリン酸化依存核転移は,ニューロンの運命を調節する.
- この経路は,神経保護とシナプス可塑性を調節するための潜在的な標的を提供します.
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