トロンビン受容体結合と活性化Rac uncapアクチンフィラメントは,浸透したヒト血小板におけるフォスフォノシチド合成を通じて刺さった端を結びます

J H Hartwig¹, G M Bokoch, C L Carpenter

¹Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.

Cell

|August 25, 1995

まとめ

RacのようなポリフォスフォノシチドとGTPーゼは,血小板内のアクチン繊維を遮断しない. 細胞シグナル伝達に不可欠なこのプロセスは,フォスホイノシチド媒介のアクチンフィラメントの開封を伴う.

科学分野:

細胞生物学細胞生物学
バイオケミストリーバイオケミストリー
分子生物学は分子生物学である.

背景:

細胞は,外部刺激に対する反応のためにアクチンポリメリゼーションを利用する.
GTPアゼは,アクチンポリメリゼーションを誘導する役割を果たします.
血小板におけるアクチン組成は,静止細胞に封じ込められたアクチン繊維 (F-アクチン) の刺さった端で起こります.

研究の目的:

血小板におけるF-アクチンの解封におけるポリフォスフォニノシチドとGTPasesの役割を調査する.
アクチンアセンブリを調節するシグナル伝達経路を解明する.

主な方法:

浸透性血小板を使用しました.
ポリフォスフォニノシチド,TRAP,GTPアナログ,GTP酵素変異体を含む様々な刺激に対するF-アクチンの解封を評価した.
フォスホイノシチド合成を測定し,開封を抑制するためにペプチドを使用しました.

主要な成果:

D3およびD4ポリフォスフォノシチド,Pl (4,5) P2を含む,休息する血小板における未加蓋のF-アクチン.
TRAP,GTP,GTPガンマSはF-アクチン解封を誘導し,GDPβSはそれを抑制した.
構成的に活性なRacはRhoではないが,活性化されたF-アクチン解封.
TRAPとRacは急速なPl{4,5) P2合成を刺激し,Pl{4,5) P2結合ペプチドは解封を阻害した.

結論:

Rac. を含むアクチンアセンブリのシグナル伝達経路を確立しました.
フォスフォノシチド媒介によるF-アクチンの解封は,この経路における重要なステップです.
この経路は,TRAP.のような刺激に対する細胞の反応に不可欠です.

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