L型カルシウムチャンネルとGSK-3は,海馬の神経細胞におけるNF-ATc4の活動を調節する

I A Graef¹, P G Mermelstein, K Stankunas

¹Department of Pathology, Howard Hughes Medical Institute, Stanford University Medical School, California 94305-5426, USA.

Nature

|October 28, 1999

まとめ

ヒポキャンパスのニューロンのカルシヌーリンは,記憶形成のための遺伝子発現を調節する. このカルシウム調節経路は,シナプス可塑性にとって極めて重要なNF-ATc4核転位を伴う.

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.
セルラー・シグナリング

背景:

学習と記憶には,カルシウム調節された遺伝子転写が含まれます.
カルシヌーリンは,カルシウム/カルモジュリン調節されたフォスファターゼで,細胞信号伝達に役割を果たします.
リンパ球では,カルシヌーリンはNF-ATc転写因子の核輸入を制御する.

研究の目的:

ヒポキャンパスのニューロンにおけるカルシヌーリンとNF-ATc4の役割を調査する.
学習と記憶形成の基礎となる分子メカニズムを解明する.

主な方法:

電気生理学的記録と,神経細胞を刺激するカリウム脱極化.
カルシウムのイメージングは,L型チャネルを通ってカルシウムの侵入を監視します.
タンパク質の転位とリン酸化を評価するために,ウェスタン・ブロッティングと免疫光.

主要な成果:

NF-ATc4は,ニューロンの活動に反応して,迅速に核に転位する.
カルシヌーリン媒介のNF-ATc4転位は,L型カルシウムチャネルに依存しています.
NF-ATc4のGSK-3リン酸化は,その転写活動を阻害する.
カルシウム/カルシヌーリン/NF-ATc経路は,イノシトール1,4,5-トリスホスファート受容体1型誘導を調節する.

結論:

カルシヌーリンのシグナル伝達は,中枢神経系におけるNF-AT媒介遺伝子発現に不可欠である.
NF-AT媒介遺伝子発現は,海馬のシナプス性可塑性および記憶に関与しています.
この経路は,記憶形成の分子基礎についての新しい洞察を提供します.

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