细胞骨激活NHE1调节机械敏感细胞体积适应和增殖
Qin Ni1, Zhuoxu Ge1, Yizeng Li2
1Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, USA.
Cell reports
|November 23, 2024
概括
阿克托米奥辛的活性通过-交换器1 (NHE1) 相互作用增加正常细胞中的细胞体积,导致核变形和生长抑制. 这种适应性反应在许多癌细胞中是不存在的.
科学领域:
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
- 分子生理学分子生理学
背景情况:
- 哺乳动物细胞通过离子和水流来调节体积,以应对环境刺激.
- 假设actomyosin收缩性可以机械控制细胞体积.
- 在细胞体积调节中actomyosin的确切作用仍然不完全理解.
研究的目的:
- 为了研究actomyosin活性影响附着哺乳动物细胞细胞体积调节的机制.
- 阐明-交换器异型1 (NHE1) 在由actomyosin介导的细胞体积变化中的作用.
- 为了确定actomyosin诱导的细胞体积变化对核结构和基因表达的下游后果.
主要方法:
- 利用了NIH 3T3和其他正常细胞系.
- 细胞接受了低心力冲击和机械拉伸.
- 测量了跨膜离子流和细胞内pH值.
- 分析了核变形和转录形状.
- 研究了NHE1和ERK信号通路的作用.
主要成果:
- 升高的actomyosin活性通过NHE1相互作用增加正常细胞中的细胞体积,导致低压性休克后缓慢的二次体积增加 (SVI).
- 机械拉伸诱导细胞内化,证实活跃的细胞反应.
- 在SVI期间细胞骨激活NHE1会使核变形,导致直接的转录基因变化和ERK依赖的生长抑制.
- 许多癌细胞系和符合基质的细胞中没有SVI和相关的核/转录组变化.
结论:
- 在细胞适应环境挑战时,actomyosin作为一种感官元素而不是仅仅是一种力量发生器.
- 动素-NHE1核轴介导一种新的细胞体积调节机制,对生长控制有影响.
- 这种机制在某些癌细胞和改变基质条件下受到损害,突出显示了它的生理相关性.
相关概念视频
Cell-matrix's Response to Mechanical Forces
2.6K
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...
2.6K
Tension Response at Adherens Junctions
2.6K
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...
2.6K
Cells Coordinate Growth and Proliferation
4.5K
Cell size is a significant factor impacting cellular design, function, and fitness. There exists some internal coordination by which cells double their masses before division, thus, achieving homeostasis. Coordination between cell growth and proliferation depends on the checkpoints in between cell cycle phases. Loss of coordination or failure in the checkpoint mechanism can drive the cell to uncontrolled growth and loss of cellular function. Like dividing cells that coordinate cellular growth,...
4.5K
Cell Motility through Blebbing
1.9K
Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
Blebbing Through the Matrix
In multicellular...
1.9K
Adaptability of Cytoskeletal Filaments
3.7K
The cytoskeleton is a complex dynamic structure performing varied functions based on cellular requirements. The adaptability of the individual filaments in the cytoskeleton determines their ability to perform various functions within the cell. It can undergo rapid reorganization during processes like cell division or remain stable for several hours as in the interphase. The adaptability of these filaments depends on stringent regulatory mechanisms. The microfilament and microtubules of the...
3.7K
Cytoskeletal Coordination in Cell Migration
4.7K
A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
4.7K


