Differentially oriented populations of actin filaments generated in lamellipodia collaborate in pushing and pausing at the cell front

Differentially oriented populations of actin filaments generated in lamellipodia collaborate in pushing and pausing at the cell front
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DOI:
10.1038/ncb1692
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发表时间:
2008-03-01
影响因子:
21.3
通讯作者:
Small, J. Victor
Small, J. Victor
中科院分区:
生物学1区
文献类型:
--
作者:
Koestler, Stefan A.;Auinger, Sonja;Small, J. Victor

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真核细胞在突起、停顿和退出阶段前进(1)。突起发生在由肌动蛋白细丝组成的斜线网络的板脂细胞中,退出终止于平行于细胞边缘的肌动蛋白束的形成。使用相关的活细胞成像和电子显微镜,我们已经表明,在突出的片层中,肌动蛋白细丝从15-90度向前倾斜,并且从突出到暂停的转变与更平行于细胞边缘的细丝的比例增加有关。肌动蛋白细丝的微棘束也显示出广泛的角状分布,相应地沿细胞前沿的两侧聚合速率也不同。我们认为,在保持结构支持所需的细丝密度的同时,片状纤毛中细丝的角位移有助于适应较慢的突起速率;此外,我们认为,单丝和微穗束有助于在突起停止时后面的片层的构建和细胞边缘的形成。我们的发现解释了荧光散斑显微镜观察到的肌动蛋白细丝在片状脂体中的可变周转动力学(2),并与当前的片状脂膜结构模型不一致,该模型以肌动蛋白细丝在树枝状阵列中70度分支为特征(3)。
eukaryotic cells advance in phases of protrusion, pause and withdrawal(1). Protrusion occurs in lamellipodia, which are composed of diagonal networks of actin filaments, and withdrawal terminates with the formation of actin bundles parallel to the cell edge. Using correlated live-cell imaging and electron microscopy, we have shown that actin filaments in protruding lamellipodia subtend angles from 15-90 degrees to the front, and that transitions from protrusion to pause are associated with a proportional increase in filaments oriented more parallel to the cell edge. Microspike bundles of actin filaments also showed a wide angular distribution and correspondingly variable bilateral polymerization rates along the cell front. We propose that the angular shift of filaments in lamellipodia serves in adapting to slower protrusion rates while maintaining the filament densities required for structural support; further, we suggest that single filaments and microspike bundles contribute to the construction of the lamella behind and to the formation of the cell edge when protrusion ceases. Our findings provide an explanation for the variable turnover dynamics of actin filaments in lamellipodia observed by fluorescence speckle microscopy(2) and are inconsistent with a current model of lamellipodia structure that features actin filaments branching at 70 degrees in a dendritic array(3).