A distinctive role for focal adhesion proteins in three-dimensional cell motility.

A distinctive role for focal adhesion proteins in three-dimensional cell motility.
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粘着斑蛋白在三维细胞运动中的独特作用。

DOI:
10.1038/ncb2062
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发表时间:
2010-06
影响因子:
21.3
通讯作者:
Wirtz, Denis
Wirtz, Denis
中科院分区:
生物学1区
文献类型:
--
作者:
Fraley, Stephanie I.;Feng, Yunfeng;Krishnamurthy, Ranjini;Kim, Dong-Hwee;Celedon, Alfredo;Longmore, Gregory D.;Wirtz, Denis

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粘着斑是在平皿上的细胞基底表面形成的大的多蛋白质组装体,其介导细胞信号传导、力传递和与基质的粘附。虽然我们对2-D系统中的粘着斑成分有很多了解,但它们在更生理性的三维(3-D)基质中迁移细胞的作用在很大程度上是未知的。活细胞显微镜显示,对于完全包埋在三维基质中的细胞,粘着斑蛋白,包括黏着斑蛋白、桩蛋白、talin、α-辅肌动蛋白、zyxin、VASP、FAK和p130 Cas,不形成聚集体,而是扩散分布在整个细胞质中。尽管没有可检测的粘着斑,粘着斑蛋白仍然调节细胞运动,但在平面基板上的细胞不同的方式。相反,黏着斑蛋白在基质包埋细胞调节细胞的速度和持久性,通过影响突起活动和基质变形,两个过程中发挥没有直接作用,在控制2-D细胞速度。这项研究表明,膜突起构成了一个关键的运动/矩阵牵引模块,驱动细胞运动的3-D矩阵。
Focal adhesions are large multi-protein assemblies that form at the basal surface of cells on planar dishes, which mediate cell signaling, force transduction, and adhesion to the substratum. While much is known about focal adhesion components in 2-D systems, their role in migrating cells within a more physiological three-dimensional (3-D) matrix is largely unknown. Live-cell microscopy shows that for cells fully embedded in a 3-D matrix, focal adhesion proteins, including vinculin, paxillin, talin, α-actinin, zyxin, VASP, FAK, and p130Cas, do not form aggregates but are diffusively distributed throughout the cytoplasm. Despite the absence of detectable focal adhesions, focal adhesion proteins still modulate cell motility but in a manner distinct from cells on planar substrates. Rather, focal adhesion proteins in matrix-embedded cells regulate cell speed and persistence by affecting protrusion activity and matrix deformation, two processes that play no direct role in controlling 2-D cell speed. This study shows that membrane protrusions constitute a critical motility/matrix-traction module that drives cell motility in a 3-D matrix.
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