アクチンネットワークは,シリアのGPCRを細胞外膀に送り込み,シグナリングを調節する
Andrew R Nager1, Jaclyn S Goldstein1, Vicente Herranz-Pérez2
1Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305-5345, USA.
Cell
|December 27, 2016
まとめ
活性化されたGタンパク質結合受容体 (GPCRs) は,アクチンを含むプロセスであるエクトサイトーシスによってシリアから放出することができます. この経路は欠陥を補償し 毛細血管の信号伝達を調節します
科学分野:
- 細胞生物学
- 分子信号
- シリアの生物学
背景:
- Gタンパク質結合受容体 (GPCRs) を含むシグナル受容体は,活性化時にシリアから出ると知られている.
- BBSome複合体は,シリアから細胞に戻す活性化受容体を媒介する.
研究 の 目的:
- BBSome-mediated retrievalが失敗すると,シリアからGPCRが活性化されるメカニズムを調査する.
- この放出プロセスに関与する細胞機構を特定する.
- この代替クリアランス経路の 生理学的および病理学的意味を理解するために
主な方法:
- 先進的な顕微鏡を用いて,目毛の先端のGPCRの振る舞いを観察する.
- アクチンおよび関連するタンパク質 (ドレブリン,ミオシン6) の受容体放出における役割の分析.
- BBSの機能と受容体回収の決定因子の遺伝的操作
- ワイルドタイプとミュータントの文脈でのヘッジホッグ信号経路の活動評価
主要な成果:
- BBSome回収を回避した活性化されたGPCRは,頭芽に蓄積され,エクトソームとして放出されます.
- アクチン,ドレブリン,ミオシン6は,エクトソーム放出プロセス (エクトサイトーシス) に不可欠である.
- シグナル依存性エクトサイトーシスは,シリアから活性化されたシグナル分子を選択的に除去します.
- エクトサイトーシスはBBSの欠陥を補償し,Bbs変異体におけるヘッジホッグ信号伝導を可能にします.
- 採取信号が欠けているキリアリア受容体は,野生型の細胞でもエクトサイトーシスを受けます.
結論:
- シグナル依存性エクトサイトーシスは,シリアから活性化されたシグナル受容体を除去するための新しい選択的メカニズムです.
- このプロセスは,正常な生理学と疾患状態の両方でシリアス信号を調節する役割を果たします.
- エクトサイトーシスは,正規の回収メカニズムが損なわれるときに,シリアリア受容体クリアランスの補償経路を提供します.
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