CaVチャネルのカルモジュリン調節における空間的なCa2+選択性のためのモジュール式スイッチ

Ivy E Dick¹, Michael R Tadross, Haoya Liang

¹Calcium Signals Laboratory, Departments of Biomedical Engineering and Neuroscience, The Johns Hopkins University School of Medicine, Ross Building, Room 713, 720 Rutland Avenue, Baltimore, Maryland 21205, USA.

Nature

|February 1, 2008

まとめ

N端の空間Ca2+変換要素 (NSCaTE) はカルモジュリンをスイッチします.

科学分野:

分子および細胞生物学
イオンチャンネル生理学イオンチャンネル生理学
カルシウムシグナル伝達

背景:

電圧誘導カルシウムチャネル (CaV) は,細胞機能にとって極めて重要です.
カルモジュリン (CaM) は,CaVチャネルと結合し,その活動を調節する.
CaMは,異なるCa2+選択性モード (ローカル対グローバル) を表しています.

研究の目的:

CaVチャネル調節における空間的なCa2+選択性の背後にあるメカニズムを調査する.
CaMのN-ロブによるローカル対グローバルCa2+センシングを決定する要因を特定する.
CaVチャネル調節における新しいNSCaTE要素の役割を明らかにする.

主な方法:

サイト・ディレクテッド・ミュータゲネシスにより,CaVチャネルにNSCaTE要素を導入/破壊する.
チャンネル活動とCa2+感受性を評価するための電気生理学的記録.
CaV1とCaV2チャネルイソフォームの比較分析.

主要な成果:

CaVチャネルのN端に位置する新しいCa2+/CaM結合部位NSCaTEは,CaMのN葉の選択性をグローバルからローカルに切り替えます.
NSCaTEが欠けているCaV2.2チャネルは,全局的なN-ロブ選択性を示すが,NSCaTEが導入されると局所的になる.
NSCaTEを持つネイティブのCaV1.2/CaV1.3チャネルは,局所的なN-ロブ選択性を示し,NSCaTEが除去されるとグローバルに破壊されます.

結論:

NSCaTEの存在または欠如は,CaV1とCaV2チャネルファミリーの間の空間的選択性の違いを説明します.
NSCaTEのN端末の位置は,CaMがチャンネルNとC端末をブリッジできると示唆しています.
NSCaTEは,CaVチャネルにおけるCa2+の選択性を理解するためのモジュールメカニズムを提供します.

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