雅丁网络中的机械应变调节了FilGAP和整体蛋白与丝A的结合
A J Ehrlicher1, F Nakamura, J H Hartwig
1Translational Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature
|September 20, 2011
概括
菲拉胺A (FLNA) 作为actin细胞骨架中的关键机械传导元素. 机械力量调节了FLNA的作用.
科学领域:
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
- 机械生物学 机械生物学
背景情况:
- 细胞对机械压力的反应对生理过程至关重要.
- 机械传导的缺陷与人体疾病 (如心力衰竭) 有关.
- 动蛋白细胞骨架传递机械力,但分子开关仍然不清楚.
研究的目的:
- 为了识别参与机械传导的actin细胞骨的分子组成部分.
- 阐明机械力如何调节细胞信号通路.
主要方法:
- 用整体和FilGAP重构一个最小的actin-FLNA系统.
- 使用光转换后的光损失 (FLOCK) 进行高速力测量.
- 在重建的系统中应用了剪切和肌肉素II驱动的力量.
主要成果:
- 菲拉胺A (FLNA) 被确定为一个中央机械传导元件.
- 机械应变增加了β-整体素与FLNA的结合.
- 机械应变导致FilGAP与FLNA分离.
结论:
- FLNA充当分子开关,将机械刺激转化为生物化学信号.
- 机械应变直接调节了信号合作伙伴与FLNA的结合.
- 这为细胞机械转导在actin细胞骨架内提供了分子基础.
相关概念视频
Generation of Straight or Branched Actin Filaments
The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Formation of Higher-order Actin Filaments
The polymerization of G-actin monomers into filamentous F-actin is a multi-step process. Once the F-actins are formed, they can bundle together in different arrangements to form higher-order networks and regulate cellular functions. Common examples include the formation of lamellipodia and filopodia at the cell's leading edge by actin reorganization in a migrating cell. The microvilli on the brush border epithelial cells are also formed through the F-actin network.
The high-order actin networks...
The high-order actin networks...
Mechanism of Filopodia Formation
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
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Actin Filament Depolymerization
Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins...
In F-actin, the ADF/cofilin proteins...
Cell-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...
Intracellular 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...


