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小胞体・筋小胞体からのリアノジン受容体を介したCa2+放出によるCa2+シグナル伝達機構の解析

佐伯 尚紀 Saeki Takanori 名古屋市立大学

2020.03.25

概要

カルシウムイオン(Ca2+)は、あらゆる細胞種においてセカンドメッセンジャーとして普遍的に働く。種々の刺激に応じた細胞質 Ca2+濃度([Ca2+]cyt)の変化は、受精や細胞増殖、細胞死、遺伝子転写、筋収縮、神経伝達物質放出、免疫反応、分泌、代謝など、極めて多彩な生理機能の調節に関与する。そのため、[Ca2+]cyt は細胞膜あるいは Ca2+貯蔵部位である小胞体やミトコンドリアなどのオルガネラの膜に発現するイオンチャネルや交換体、ポンプによって精緻な制御を受けている。Na+や K+、Cl-といった他のイオンの細胞質濃度が mM オーダーであるのに対して、通常時の[Ca2+]cyt は数十 nM から百 nM 程度という非常に低い濃度に保たれており、細胞外 Ca2+とは一万倍以上の濃度勾配を形成している。刺激入力時には数百 nM から数十μM の範囲で [Ca2+]cyt が上昇し、シグナル分子として機能する。

Ca2+シグナルは、[Ca2+]cyt 変化の様子や持続時間あるいは Ca2+を透過する分子実体や活性化機構に基づいて、Ca2+ウェーブやCa2+オシレーション、Ca2+スパーク、Ca2+パフ、 Ca2+ホットスポット、Ca2+誘発性 Ca2+放出、ストア作動性Ca2+流入など様々な分類がされている。このように、[Ca2+]cyt 変化が時間的(ミリ秒~日単位)・空間的(ナノ~ミリメートル単位)に制御されることで、多様な Ca2+シグナル伝達が成立することが明らかにされてきた(図 1)(1)。

本研究では、小胞体および筋小胞体の膜上に発現する Ca2+透過チャネルのリアノジン受容体(RyR)によって形成される「Ca2+オシレーション」と「Ca2+スパーク」という 2つの異なる性質を持つCa2+シグナルに着目した。

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