ESCRT複合体による多胞体生物発生の分子機構

Thomas Wollert¹, James H Hurley

¹Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland 20892, USA.

Nature

|March 23, 2010

まとめ

輸送 (ESCRT) 機械に必要なエンドソーム分別複合体は,多胞体体の形成を駆動する. ESCRT-IとESCRT-IIは膜芽を作り,ESCRT-IIIは膜芽の分裂を介し,内小胞を形成する.

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:

多細胞体 (MVB) は,細胞内分類と分解に不可欠です.
輸送用機械 (ESCRT) に必要とされるエンドソーム分別複合体は,MVBの生殖に関与しています.
ESCRTによる膜芽生えと分裂の正確なメカニズムは,まだ完全に理解されていません.

研究の目的:

ESCRT媒介の多胞体生物発生のステップ・バイ・ステップメカニズムを解明する.
膜変形および膀形成における個々のESCRT複合体の役割を視覚化および特徴づけること.
貨物がどのように分類され,内小胞に組み込まれているかを理解する.

主な方法:

巨大なユニラメラー膀 (GUVs) を用いてMVB生殖を再構成する.
ESCRT-0, -I, -II,および -III複合体の光ラベルを使用しました.
模範貨物として,膜結合型光ユビキチン融合を使用した.

主要な成果:

ESCRT-0は貨物を集中させるが,膜変形を引き起こさない.
ESCRT-IとESCRT-IIは協力して膜を芽に変形させ,貨物を閉じ込めます.
ESCRT-IIIは,結合することなく,芽を効率的に割って,内膀を形成します.
このプロセスは,エンドソーム膜の細胞質側から発生します.

結論:

ESCRTの仕組みは,ESCRT-0,-I/II,および-IIIの異なる役割を通して,次々にMVPの形成を推進します.
ESCRT-I/IIは,膜の芽生えと貨物の徴集を担当しています.
ESCRT-IIIは最終的な分裂イベントを媒介し,内膀を放出します.
このメカニズムは,ESCRTの消費なしに,効率的な貨物の分類と劣化を可能にします.

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