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関連する概念動画

Ligand Binding Sites02:40

Ligand Binding Sites

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Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
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Cell-matrix's Response to Mechanical Forces01:13

Cell-matrix's Response to Mechanical Forces

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In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
Anchoring junctions mechanically attach a cell to the...
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Types of Signaling Molecules01:32

Types of Signaling Molecules

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In multicellular organisms, many molecules transmit signals between cells to pass information. These signals vary in complexity and include small peptides, nucleotides, steroids, fatty acid derivatives, and dissolved gases such as nitric oxide. Some signaling molecules diffuse through the plasma membrane to act locally between neighboring cells or travel long distances. Others remain attached to the cell surface, transmitting information to other cells only when they make contact. In some...
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Selectins01:25

Selectins

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Cell adhesion is  an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain,...
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Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
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Activation of Integrins

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Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
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フォースロードは,細胞によるリガンドの空間感知を説明する.

Roger Oria1,2, Tina Wiegand3,4, Jorge Escribano5

  • 1Institute for Bioengineering of Catalonia (IBEC), the Barcelona Institute of Technology (BIST), 08028 Barcelona, Spain.

Nature
|December 7, 2017
PubMed
まとめ

細胞は細胞外マトリックス (ECM) リガンドの配置によって環境を感知する. この間隔は直接的な測定ではなく 細胞粘着とYAPの調節に影響し 細胞の行動に影響します

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科学分野:

  • 細胞生物学
  • バイオ物理学
  • 材料科学

背景:

  • 細胞はインテグリンを通して細胞外マトリックス (ECM) と相互作用し,物理的性質を感知する.
  • 以前の研究では,細胞がナノメートルスケールのリガンド間隔を使用して粘着を調節することを示唆しており,これは分子ルラーメカニズムを暗示しています.
  • インテグリン媒介の粘着と焦点粘着形成は,細胞機能にとって極めて重要であり,物理的な微環境によって影響を受けます.

研究 の 目的:

  • 細胞がECMリガンドの距離と基板の硬さをどのように感知するかを調査する.
  • 物理的なシグナルに反応する焦点粘着形成と調節の背後にあるメカニズムを解明する.
  • YAPの転写調節におけるリガンド分布と基板メカニズムの役割を調査する.

主な方法:

  • 制御されたECMリガンド密度と間隔を持つ調節可能なヒドロゲル基板の開発
  • 焦点粘着力学と細胞形態学の観察のための顕微鏡技術.
  • インテグリン-ECMの相互作用をシミュレートするために,拡張分子クラッチモデルを使用した計算モデリング.
  • 細胞の牽引力とアクチン流速の測定

主要な成果:

  • 焦点粘着の成長は,低硬度基板のリガンド間隔の増加によって促進されるが,高硬度基板の粘着崩壊につながる.
  • リガンド分布の乱れは,粘着の増幅を促すが,崩壊のための剛性の値を下げる.
  • YAP (Yes-associated protein) の局所化 (核または細胞) は,焦点結合の成長と崩壊と相関しています.
  • 分子クラッチモデルは,フォース・ロードとインテグリン・リクルートメントに基づいて観察された粘着ダイナミクスを正確に予測します.

結論:

  • ECMの空間情報に対する細胞の感知は,直接的なリガンド間隔測定ではなく,力に依存するインテグリン採用と再分配によって媒介される.
  • 基板の剛性とリガンドの分布は,焦点粘着形成,安定性,およびYAP媒介による転写調節を制御するために相互作用する.
  • この研究は 細胞内のナノスケール物理感知を理解するための枠組みを提供し 生物学的プロセスに不可欠です