BBSタンパク質のコア複合体は,GTPase Rab8と協力して,シリア膜バイオゲネシスを促進します

Maxence V Nachury¹, Alexander V Loktev, Qihong Zhang

¹Genentech, Inc., South San Francisco, CA 94080, USA. nachury@gene.com

Cell

|June 19, 2007

まとめ

BBSomeとして知られるBardet-Biedl症候群 (BBS) 複合体は,一次性シリア形成に不可欠である. この複合体の欠陥は,膀輸送を妨害し,BBSの症状を引き起こす.

科学分野:

分子生物学は分子生物学である.
細胞生物学細胞生物学
遺伝学遺伝学とは

背景:

主要なシリウム機能不全は,バルデット-ビエル症候群 (BBS) の病原性にとって中心的なものです.
BBSの症状には,肥満,網膜変性,腎不全があります.
特定された12のBBS遺伝子にもかかわらず,BBSの分子基盤は不明のままである.

研究の目的:

バーデット・ビドル症候群の分子基礎を解明するため.
シリオゲネシスにおけるBBSタンパク質の機能を特定するために.

主な方法:

7つの保存されたBBSタンパク質 (BBSome) の複合体の識別と特徴付け.
サイトプラズマ構造とプライマリシリアにおけるBBSomeの局所化研究.
BBSome機能とシリオゲネシスにおけるRab8 GDP/GTP交換因子の役割を調査した.
破壊されたシリオゲネシスのインビボインパクトを評価するためにゼブラフィッシュモデルを使用しました.

主要な成果:

7つのタンパク質からなる複合体であるBBSomeが特定され,中心の衛星と膜に局所化されました.
BBSomeはシリオゲネシスには不可欠ですが,中心衛星機能には欠かせません.
基礎体にあるBBSomeと相互作用するRab8 GTPaseは,プライマリシリウム膜の拡張に不可欠です.
Rab8 (GTP) 生産の抑制は,シリオゲネシスを阻害し,ゼブラフィッシュでBBSのフェノタイプを誘導しました.

結論:

BBSomeは,膀の輸送を媒介することによって,一次シリアの形成に重要な役割を果たします.
BBSのいくつかの欠陥により,主シリウムへの機能不全の膀輸送は,おそらくバーデット-ビデル症候群を引き起こす.
BBSome-Rab8経路を標的にすることは,BBSに対する潜在的な治療の道を提供します.

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