Self-organized podosomes are dynamic mechanosensors.

Self-organized podosomes are dynamic mechanosensors.
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DOI:
10.1016/j.cub.2008.07.046
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发表时间:
2008-09-09
期刊:
影响因子:
9.2
通讯作者:
Wang, Ning
Wang, Ning
中科院分区:
生物学1区
文献类型:
--
作者:
Collin, Olivier;Na, Sungsoo;Chowdhury, Farhan;Hong, Michael;Shin, Myung Eun;Wang, Fei;Wang, Ning

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Podosomes是一种自组织的动态肌动蛋白结构,通过整合素粘附在细胞外基质上。然而,目前尚不清楚是什么调节了足体动力学,以及足体是否可以像局灶性粘连一样作为直接的机械传感器发挥作用。我们在这里表明,肌球蛋白II形成环形结构外,并在podosome肌动蛋白环调节podosome动力学。抑制肌球蛋白II依赖性张力消散的肌球蛋白环结构之前,消散的足状体肌动蛋白环。由于足体环的大小或形状发生变化,足体下方的牵引力被施加到底物上,当肌球蛋白轻链活性被抑制时,牵引力被消除。牵引力的大小与局部粘连下方产生的牵引力相当,并随基质硬度增加而增加。podosomes和局灶性粘连的动力学是不同的。在不运动和不旋转的细胞中,通过旋转足体环产生足体环下方的扭转牵引力,这表明这些圆形结构具有独特的特征。通过整合素在顶面施加的应力直接使基底面附近的podosomes移位。应力诱导的足体位移随应力的增加呈非线性增加。我们的研究结果表明,podosomes是动态力学传感器,其中肌球蛋白张力和肌动蛋白动力学的相互作用是至关重要的,在活细胞中调节这些自组织结构。
Podosomes are self-organized dynamic actin-containing structures that adhere to the extracellular matrix via integrins. Yet it is not clear what regulates podosome dynamics and whether podosomes can function as direct mechanosensors like focal adhesions. We show here that myosin IIs form circular structures outside and at the podosome actin ring to regulate podosome dynamics. Inhibiting myosin II-dependent tension dissipated podosome actin rings before dissipating the myosin ring structure. As podosome rings changed size or shape, tractions underneath the podosomes were exerted onto the substrate, which were abolished when myosin light chain activity was inhibited. The magnitudes of tractions were comparable to those generated underneath focal adhesions and increased with substrate stiffness. The dynamics of podosomes and of focal adhesions were different. Torsional tractions underneath the podosome rings were generated with rotations of podosome rings in a non-motile and non-rotating cell, suggesting a unique feature of these circular structures. Stresses applied via integrins at the apical surface directly displaced podosomes near the basal surface. Stress-induced podosome displacements increased nonlinearly with applied stresses. Our results suggest that podosomes are dynamic mechanosensors in which interactions of myosin tension and actin dynamics are crucial in regulating these self-organized structures in living cells.
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