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Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
ノッチとデルタの間のCis相互作用は,相互に排他的なシグナル状態を生成します.
David Sprinzak1, Amit Lakhanpal, Lauren Lebon
1Howard Hughes Medical Institute, Division of Biology and Department of Applied Physics, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA.
Nature
|April 27, 2010
まとめ
Notch-Deltaシグナル伝達経路は,細胞通信のために cis 阻害とトランス活性化を使用します. この研究は,超敏感なスイッチメカニズムが,発達中の組織でパターン形成を促すことを示しています.
科学分野:
- 細胞生物学と発達生物学について
- バイオフィジックス 生物物理学
- システム生物学 システム生物学
背景:
- Notch-Delta信号伝達経路は,発達中の細胞間の通信に不可欠であり,細胞の運命決定と組織パターンを調節します.
- デルタリンガンドは,隣接する細胞でNotchをトランス活性化し,同じ細胞でNotchをシス抑制する二重の活性を示しています.
- これらの二重活動の統合とパターン形成における役割は,まだ完全に理解されていません.
研究 の 目的:
- 個々の哺乳類の細胞におけるノッチ・デルタ信号伝達の定量的なダイナミクスを調査する.
- システムがどのようにシス・デルタとトランス・デルタの活動を統合して,パターン形成を実現するかを明らかにする.
- ノッチ・デルタシステムの入力・出力関係を理解するために.
主な方法:
- ノッチ・デルタ信号ダイナミクスのリアルタイム分析のための定量的なタイムラップ顕微鏡プラットフォームの開発.
- cis-およびtrans-Delta濃度の制御された操作.
- Notch レポーターのダイナミクスを監視し,システムの応答を測定します.
主要な成果:
- トランス-デルタに対するノッチ反応はグレード化され,シス-デルタに対する反応は急性であり,値に依存しています.
- 数学的モデルにより,ノッチタンパク質とデルタタンパク質の相互無効化により,超敏感なスイッチが作られることが示されました.
- このスイッチは,細胞間の差異の増幅と,鋭い境界線と横の阻害パターンの形成を可能にします.
結論:
- Notch-Deltaシステムは,超敏感なスイッチとして機能し,相互タンパク質の無活性化によってパターン形成を促進します.
- このメカニズムは,発達中に鋭い境界線と横向的な阻害パターンがどのように出現するかを説明します.
- 発見は,発達過程と以前説明できなかった突然変異の現象型についての洞察を提供します.
関連する概念動画
01:19Contact-dependent Signaling
Contact-dependent signaling, as the name suggests, requires that communicating cells be in direct contact with each other. This is achieved either through receptor-ligand interactions or by specialized cytoplasmic channels that allow the flow of small molecules between cells. In animal cells, channels called gap junctions facilitate contact-dependent signaling in certain tissues, whereas, plasmodesmata perform a similar function in plants.
Gap Junctions
In animal cells, gap junctions are formed...
Gap Junctions
In animal cells, gap junctions are formed...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
02:33Hedgehog Signaling Pathway
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...