Actin-dependent lamellipodia formation and microtubule-dependent tail retraction control-directed cell migration
Actin-dependent lamellipodia formation and microtubule-dependent tail retraction control-directed cell migration
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DOI：
10.1091/mbc.11.9.2999
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发表时间：
2000-09-01
影响因子：
3.3
通讯作者：
Imhof, BA
中科院分区：
文献类型：
--
作者：
Ballestrem, C;Wehrle-Haller, B;Imhof, BA
迁移的细胞是极化的，在细胞前面有一个膨胀的薄片，然后是细胞的主体，在细胞的后面有一个可伸缩的尾巴。板层终止于面向迁移方向的褶皱板状伪足。虽然肌动蛋白在板状伪足形成中的作用已经得到了很好的证实，但微管在这一过程中的作用程度还不清楚。在此，我们研究了微管的贡献，细胞运动的延时视频显微镜上的绿色荧光蛋白-肌动蛋白和微管蛋白-绿色荧光蛋白转染的黑色素瘤细胞。用微管破坏剂诺考达唑或用稳定剂紫杉醇处理细胞显示出减少的皱褶和板状伪足形成。然而，这并不是由于内在的不能形成皱褶和片状伪足，因为两者都恢复了刺激细胞与佛波醇12-肉豆蔻酸酯13-乙酸在一个Rac依赖的方式，并通过干细胞因子在黑素细胞表达受体酪氨酸激酶c-kit。虽然皱褶和板状伪足的形成没有微管，微管网络是需要毛皮的细胞体的前进和随后的尾部缩回。总之，我们表明，形成片状伪足可以发生通过肌动蛋白聚合独立的微管，但微管所需的细胞迁移，尾部收缩，和调制的细胞粘附。
Migrating cells are polarized with a protrusive lamella at the cell front followed by the main cell body and a retractable tail at the rear of the cell. The lamella terminates in ruffling lamellipodia that face the direction of migration. Although the role of actin in the formation of lamellipodia is well established, it remains unclear to what degree microtubules contribute to this process. Herein, we have studied the contribution of microtubules to cell motility by time-lapse video microscopy on green flourescence protein-actin- and tubulin-green fluorescence protein-transfected melanoma cells. Treatment of cells with either the microtubule-disrupting agent nocodazole or with the stabilizing agent taxol showed decreased ruffling and lamellipodium formation. However, this was not due to an intrinsic inability to form ruffles and lamellipodia because both were restored by stimulation of cells with phorbol 12-myristate 13-acetate in a Rac-dependent manner, and by stem cell factor in melanoblasts expressing the receptor tyrosine kinase c-kit. Although ruffling and lamellipodia were formed without microtubules, the microtubular network was needed fur advancement of the cell body and the subsequent retraction of the tail. In conclusion, we demonstrate that the formation of lamellipodia can occur via actin polymerization independently of microtubules, but that microtubules are required for cell migration, tail retraction, and modulation of cell adhesion.