The Action of Small GTPases Rab11 and Rab25 in Vesicle Trafficking During Cell Migration
The Action of Small GTPases Rab11 and Rab25 in Vesicle Trafficking During Cell Migration
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DOI：
10.1159/000295249
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发表时间：
2012-01-01
影响因子：
--
通讯作者：
Jendrossek, Verena
中科院分区：
文献类型：
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作者：
Kessler, Daniel;Gruen, Gianna-Carina;Jendrossek, Verena
背景：GTP酶Rab 11和Rab 25通过调节囊泡转运和表面受体的再循环促进细胞迁移。Rab 25在其GT3结构域中携带组成型激活突变。Rab 25的表达增加与迁移性肿瘤细胞的侵袭性有关。在这里，我们的目的是阐明这两个GTP酶在细胞迁移过程中的囊泡运输的作用的潜在差异。研究方法：我们在HeLa和MDA-MB 231细胞中表达Rab 11和Rab 25野生型和突变型构建体，并测量它们对细胞形态、囊泡动力学和迁移行为的影响。在前列腺癌样品中，我们分析了两种GTP酶的表达。结果如下：当Rab 11失活时，在纤连蛋白上生长的细胞显示出更拉伸的形态，而Rab 25的失活导致拉伸减少。Rab 11和Rab 25的过表达促进了细胞迁移。囊泡运动的分析显示Rab 11阳性囊泡在细胞内室中的运输效率较高，Rab 25阳性囊泡在膜附近的运输效率较高。有趣的是，我们发现Rab 25在前列腺癌组织中高度表达。结论：综上所述，我们的数据表明，Rab 11主要负责从后端到前端的迁移细胞的基础长距离运输，而Rab 25主要作用于细胞尖端内的小规模快速再循环。我们的结果进一步支持Rab 25作为肿瘤发展促进剂的想法。版权所有（c）2012 S. Karger AG，巴塞尔
Background: The closely related GTPases Rab11 and Rab25 promote cell migration by regulating vesicular transport and recycling of surface receptors. Rab25 carries a constitutively activating mutation in its GTPase domain. Increased expression of Rab25 has been associated with the aggressiveness of migrating tumor cells. Here, we aimed to elucidate potential differences in the role of those two GTPases in vesicle trafficking during cell migration. Methods: We expressed Rab11 and Rab25 wildtype and mutant constructs in HeLa and MDA-MB231 cells and measured their effect on cell morphology, vesicle dynamics and migration behaviour. In prostate cancer samples we analyzed the expression of both GTPases. Results: Cells grown on fibronectin displayed a more stretched morphology when Rab11 was inactivated, whereas inactivation of Rab25 led to reduced stretching. Overexpression of both Rab11 and Rab25 accelerated cell migration. Analysis of vesicular movement revealed higher transport efficiency in the inner cell compartment for Rab11 positive vesicles and in proximity to the membrane for Rab25 positive vesicles. Interestingly, we found Rab25 to be highly expressed in prostate cancer tissue. Conclusion: Taken together, our data suggest that Rab11 is mainly responsible for basal long-distance transport from the rear end to the front of the migrating cell, whereas Rab25 acts predominantly in the small-scale fast recycling within the tips of the cell. Our results further support the idea of Rab25 as a promoter of tumor development. Copyright (c) 2012 S. Karger AG, Basel