National Centre for Cell Science, Ganeshkhind, Pune, India.
PLoS One. 2015 Apr 20;10(4):e0125506. doi: 10.1371/journal.pone.0125506. eCollection 2015.
Ran, a member of the Ras-GTPase superfamily, has a well-established role in regulating the transport of macromolecules across the nuclear envelope (NE). Ran has also been implicated in mitosis, cell cycle progression, and NE formation. Over-expression of Ran is associated with various cancers, although the molecular mechanism underlying this phenomenon is unclear. Serendipitously, we found that Ran possesses the ability to move from cell-to-cell when transiently expressed in mammalian cells. Moreover, we show that the inter-cellular transport of Ran is GTP-dependent. Importantly, Ran displays a similar distribution pattern in the recipient cells as that in the donor cell and co-localizes with the Ran binding protein Nup358 (also called RanBP2). Interestingly, leptomycin B, an inhibitor of CRM1-mediated export, or siRNA mediated depletion of CRM1, significantly impaired the inter-cellular transport of Ran, suggesting a function for CRM1 in this process. These novel findings indicate a possible role for Ran beyond nucleo-cytoplasmic transport, with potential implications in inter-cellular communication and cancers.
Ran 是 Ras-GTPase 超家族的成员，在调节核膜（NE）上大分子的运输方面具有既定的作用。Ran 也与有丝分裂、细胞周期进程和 NE 形成有关。Ran 的过表达与各种癌症有关，尽管这种现象的分子机制尚不清楚。偶然地，我们发现 Ran 具有在哺乳动物细胞中瞬时表达时在细胞间移动的能力。此外，我们表明 Ran 的细胞间转运依赖于 GTP。重要的是，Ran 在受体细胞中的分布模式与供体细胞中的分布模式相似，并且与 Ran 结合蛋白 Nup358（也称为 RanBP2）共定位。有趣的是，CRM1 介导的出口抑制剂莱普霉素 B 或 siRNA 介导的 CRM1 耗竭显著损害了 Ran 的细胞间转运，表明 CRM1 在该过程中具有功能。这些新发现表明 Ran 在核质转运之外可能具有潜在的作用，这可能对细胞间通讯和癌症产生影响。
