核通过FHOD相关的LINC复合体激活机械反应
bioRxiv : the preprint server for biology
|July 15, 2025
概括
细胞核活跃地指导着actin细胞骨架的机械特性. 这种核功能中断可能导致心脏缩.
科学领域:
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
- 心血管研究研究心血管研究
背景情况:
- 核,一个关键的真核细胞器官,传统上被视为细胞信号的被动接收器.
- 它在积极影响细胞机械环境中的作用是不太了解的.
研究的目的:
- 研究核在指导actin细胞骨架的机械性质中的积极作用.
- 探索FHOD形式素和LINC复合体在这一过程中的参与.
- 检查核机械调节中断在心脏病中的后果.
主要方法:
- 生物化学试验,以评估FHOD形式素的actin捆绑活性.
- 使用纤维细胞和心肌细胞进行细胞研究,以分析与核结合的活性电缆.
- 在体内研究使用具有特定FHOD3等位基因的小鼠模型.
主要成果:
- 当与LINC复合体相互作用时,FHOD形式素表现出强烈的活性.
- 核接的活性电缆在具有FHOD相关LINC复合体的细胞中显示出增强的机械电阻.
- 与多变性心肌病相关的FHOD3变体损害了这些机械调节过程.
- 具有FHOD3 R637P等位基因的小鼠模型表明胚胎致死性和压力诱导的心脏缩.
结论:
- 核积极指导其机械环境,挑战被动响应模型.
- 心脏中这种核介导机械控制的失调有助于心脏缩.
- FHOD3和LINC复合体对于核机械调节和预防心脏病理至关重要.
更多相关视频
09:43A Protocol for Using Förster Resonance Energy Transfer (FRET)-force Biosensors to Measure Mechanical Forces across the Nuclear LINC Complex
Published on: April 11, 2017
10.8K
05:47A Direct Force Probe for Measuring Mechanical Integration Between the Nucleus and the Cytoskeleton
Published on: July 29, 2018
15.9K
相关概念视频
Cell-matrix's Response to Mechanical Forces
2.8K
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...
2.8K
Tension Response at Adherens Junctions
2.9K
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
2.9K
Mechanism of Filopodia Formation
2.5K
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...
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...
2.5K
Mechanically-gated Ion Channels
6.7K
Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
6.7K
Intracellular Signaling Affects Focal Adhesions
2.8K
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...
2.8K
Anchoring Junctions
4.0K
Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...
4.0K
