Dynamics of contacts between lamellae of fibroblasts: Essential role of the actin cytoskeleton

Dynamics of contacts between lamellae of fibroblasts: Essential role of the actin cytoskeleton
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DOI:
10.1073/pnas.95.8.4362
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发表时间:
1998-04-14
影响因子:
11.1
通讯作者:
Gelfand, IM
Gelfand, IM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Gloushankova, NA;Krendel, MF;Gelfand, IM

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我们研究了未转化成纤维细胞和癌基因转化成纤维细胞主板碰撞过程中肌动蛋白、细胞骨架和黏附分子的动态变化。用实时电子显微镜观察发现,在板层碰撞过程中,前导板层有相当多的重叠,随后发生收缩,未转化的成纤维细胞重叠时,形成与细胞长轴平行的β-连环素阳性接触结构,这些结构与肌动蛋白细丝束相关。这种细胞接触结构的维持关键依赖于肌动蛋白细胞骨架的收缩能力,因为用无血清培养液或2,3-丁二酮2-单肟(BDM)抑制收缩能力会导致链形成的丧失。当无血清培养液中的细胞与微管抑制剂诺康唑孵育时,链的形成得以恢复,诺康唑被认为可以增加收缩能力。癌基因转化的成纤维细胞对碰撞的反应类似于未转化的成纤维细胞,但没有形成良好的细胞-细胞接触。提出了一个模型来描述肌动蛋白细胞骨架组织的差异如何解释极化的成纤维细胞和非极化的上皮细胞对细胞-细胞接触的结构上的不同反应。
We investigated actin cytoskeletal and adhesion molecule dynamics during collisions of leading lamellae of nontransformed and oncogene-transformed fibroblasts. By using real-time,ideo microscopy, it was found that during lamellar collision there peas considerable overlapping of leading lamellae followed by subsequent retraction, Overlapping of nontransformed fibroblasts was accompanied by formation of beta-catenin-positive contact structures organized into strands oriented parallel to the long axis of the cell that were associated with bundles of actin filaments. Maintenance of such cell-tell contact structures critically depended on the contractility of actin cytoskeleton, as inhibition of contractility with serum-free medium or 2,3-butanedione 2-monoxime (BDM) resulted in loss of strand formation. Strand formation was recovered when cells in serum-free medium were incubated with the microtubule inhibitor nocodazole, which is known to increase contractility. Oncogene-transformed fibroblasts reacted to collisions with responses similar to nontransformed fibroblasts but did not develop well-organized cell-cell contacts. A model is presented to describe how differences in the organization of the actin cytoskeleton could account for the structurally distinct responses to cell-cell contact by polarized fibroblastic cells versus nonpolarized epithelial cells.