キナーゼ調節されたPDZドメイン相互作用は,β2-アドレナージック受容体の内細胞的分類を制御する

T T Cao¹, H W Deacon, D Reczek

¹Department of Biochemistry and Biophysics, University of California, San Francisco 94143, USA.

Nature

|September 28, 1999

まとめ

PDZドメインとアクチンは,エンドソームにおけるβ2-アドレナジック受容体の分類を調節する. GRK-5によるリン酸化は,この相互作用を制御し,受容体輸送と信号伝導に影響を与えます.

科学分野:

細胞生物学細胞生物学
分子生物学は分子生物学である.
メンブラン取引メンブラン取引

背景:

膜タンパク質が内細胞経路でどのように分類されているかを理解することは,細胞生物学にとって極めて重要です.
内部化されたβ2-アドレナリン受容体の分類は,信号伝導に影響を与え,刺激によって調節されます.

研究の目的:

腸内細胞経路におけるβ2-アドレナリン受容体の分類を制御するメカニズムを解明する.
この過程におけるPDZドメイン,EBP50,アクチン細胞骨格の役割を調査する.

主な方法:

EBP50,β2-アドレナリン受容体,アクチン細胞骨格との相互作用を研究した.
EBP50の相互作用とアクチンのポリメリゼーションを阻害し,受容体の分類に及ぼす影響を観察した.
受容体-EBP50の相互作用とリサイクルにおけるセリン411のリン酸化の役割を分析した.

主要な成果:

EBP50は,PDZドメイン経由でβ2-アドレナリン受容体と,ERM結合ドメイン経由でアクチン細胞骨格と結合する.
EBP50の相互作用またはアクチン細胞骨格の破壊は,β2-アドレナリン受容体のミソソート化を引き起こしますが,トランスファーリン受容体は起こしません.
GRK-5によるβ2-アドレネルゲン受容体尾のセリン411のリン酸化は,EBP50の相互作用と適切なリサイクルに不可欠です.

結論:

PDZドメイン媒介の相互作用とアクチン細胞骨格は,内細胞分類において重要な役割を果たします.
GRK-5媒介のリン酸化は,内分細胞分裂後のGタンパク質結合受容体の膜輸送を調節する.

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