インテグリンとノッチシグナリングを活性化するために必要な単一の分子力を定義する
1Department of Physics, Center for the Physics of Living Cells and Institute for Genomic Biology University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Science (New York, N.Y.)
|May 25, 2013
まとめ
研究者は,細胞が環境と相互作用するために使用する力を測定するための新しい方法を開発しました. 彼らは,細胞がインテグリン-リガンド結合に約40ピコニュートン,ノッチ受容体を活性化するために12pN未満を適用することを発見しました.
科学分野:
- 細胞力学 細胞力学
- 分子生物学は分子生物学である.
- バイオフィジックス 生物物理学
背景:
- 細胞の機能と多細胞の発達は,膜受容体による機械的相互作用に依存しています.
- 単一分子力の理解は,受容体-リガンド信号伝達経路の解読に不可欠です.
研究 の 目的:
- 単一リガンド受容体結合を活性化するために必要な精密な力を測定する方法を開発する.
- 細胞が初期結合と受容体活性化時に施す力学的力を定量化するために.
主な方法:
- テンションゲージテザー (TGT) アプローチを開発し,破裂性テザーを介してリガンドを不動化する.
- 受容器-リガンドの緊張を制限するために,調節可能な張力許容量を持つテザーを使用しました.
- インテグリン-リガンド結合とノッチ受容体に対する力を測定するためにTGTを適用した.
主要な成果:
- 細胞は,初期結合中の単一インテグリン-リガンド結合に約40ピコニュートン (pN) の普遍的なピークテンションを適用します.
- Notch受容体の活性化には,12pN未満の力が必要です.
- TGTアプローチは,細胞機能を調節するために,定義された分子力学的シグナルを提供することができます.
結論:
- TGTメソッドは,細胞結合とシグナル伝達における単一分子力を正確に測定します.
- 特定の力の値は,インテグリンやノッチなどの重要な細胞受容体の活性化に不可欠です.
- この技術は,機械伝導を調査し,細胞の行動を制御するための新しいツールを提供します.
関連する概念動画
01:15Activation of Integrins
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 events provide an effective stimulus.
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 events provide an effective stimulus.
01:17Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
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...
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...
01:10Integrins
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
01:13Cell-matrix's Response to Mechanical Forces
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...
Anchoring junctions mechanically attach a cell to the...