カルシウムチャネルによる連続的なイオンおよび構成信号は,ニューロンの遺伝子発現を誘導する
Boxing Li1, Michael R Tadross2, Richard W Tsien3
1Department of Neuroscience and Physiology and New York University Neuroscience Institute, New York, NY 10016, USA.
Science (New York, N.Y.)
|February 26, 2016
まとめ
電圧ゲート型CaV1.2チャネルには,カルシウムイオン (Ca2+) の流入と電圧依存型変形 (VΔC) の両方が必要である. これらの信号の正確な順番は 遺伝子転写の活性化に不可欠です
科学分野:
- 神経科学
- 分子生物学
- バイオ物理学
背景:
- Voltage-gated CaV1.2チャネルは 神経の可塑性の鍵となるものです
- カルシウムの流入と電圧に依存する形状の変化を含むCaV1.2のシグナルメカニズムは不明である.
研究 の 目的:
- Ca2+ 流入と電圧依存型変化 (VΔC) のCaV1.2 チャンネル関数の異なる役割を解明する.
- CaV1.2によって媒介される転写依存神経の可塑性に対するシグナル要求を決定する.
主な方法:
- 独立した信号制御のためにCaV1.2をリガンドゲートされたCa2+浸透性チャネルに結合する融合タンパク質を設計した.
- Ca2+とVΔC信号のタイミングと存在を操作して,その転写への影響を評価した.
主要な成果:
- CaV1.2は連続的なシグナルメカニズムを必要とします:Ca2+の流入はCa2+/カルモジュリン依存タンパク質キナーゼII (CaMKII) を動員し,VΔC媒介による蓄積が続く.
- Ca2+ も VΔC も単独ではトランスクリプションの活性化には不十分であり,Ca2+ が VΔC の10〜20秒前に発生したときに最適の活性化が生じた.
- VΔCはN-メチル-D-アスパルテート受容体のシグナル伝達を相乗的に強化し,その機能障害はティモシー症候群における自閉症の症状と相関していた.
結論:
- 非イオン型VΔC信号は,シナプス可塑性および神経精神学的プロセスにおけるCaV1.2チャネル機能に不可欠である.
- CaV1.2は,Ca2+とVΔCの両方を含む二重,順序依存のシグナル伝達経路を通じて,転写依存の神経の可塑性を媒介する.
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