微生物誘発のGTPase極性回路におけるダイナミックハブとしてのF-アクチンの特定
Robert C Orchard1, Mark Kittisopikul, Steven J Altschuler
1Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cell
|February 21, 2012
まとめ
バクテリアの病原体は,F-actinと相互作用するグアニン-ヌクレオチド交換因子 (GEF) を使用して細胞の極性を乗っ取ります. この相互作用はCdc42 GTPaseの偏分を駆動し,哺乳類と細菌の細胞の偏分に関する保存されたメカニズムを明らかにします.
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
- 微生物学 微生物学とは
背景:
- 細胞の極性は哺乳類の細胞機能にとって極めて重要であり,複雑な信号ネットワークによって調節されます.
- 細菌の病原体は,これらの宿主細胞経路を自分の利益のために操作することができます.
研究 の 目的:
- 哺乳類の細胞の極性および細菌の病原性の基本原理を明らかにする.
- Cdc42のGTPaseシグナル伝達における腸病原性Escherichia coliのグアニン-ヌクレオチド交換因子 (GEF) の役割を調査する.
主な方法:
- 扱える実験的,理論的モデルの開発.
- 地図GEFの合成派生物を利用した.
- アクチンダイナミクスとフィードバックループを分析するために数学的モデリングを使用しました.
主要な成果:
- Cdc42 GTPase信号伝導がMap GEFとF-actin.との相互作用によって制御されていることが発見されました.
- アクチンダイナミクスとMAP依存の陽性フィードバックループが,プラズマ膜上で自発的にCdc42を極化することを示した.
- β-インテグリンを刺激するためにシグナル回路を再配線することで,細胞外シグナルへの反応としてCdc42の極化が可能であることを示した.
結論:
- GEFsとF-actin.の相互作用を中心に細胞の極性のための分子経路を提案しました.
- このメカニズムは保存されていて,哺乳類の細胞や細菌感染を含む多様な生物系で機能している可能性が高い.
関連する概念動画
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Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
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Three regulatory proteins control their activity:
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Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
GPCRs Regulate Adenylyl Cylase Activity
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