Department of Biology and Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
Mol Biol Cell. 2011 Apr;22(7):1045-57. doi: 10.1091/mbc.E10-06-0519. Epub 2011 Feb 9.
Tubulin posttranslational modifications (PTMs) have been suggested to provide navigational cues for molecular motors to deliver cargo to spatially segregated subcellular domains, but the molecular details of this process remain unclear. Here we show that in Madin-Darby Canine Kidney (MDCK) epithelial cells, microtubules express several tubulin PTMs. These modifications, however, are not coordinated, and cells have multiple subpopulations of microtubules that are marked by different combinations of PTMs. Furthermore these subpopulations show differential sensitivity to both drug- and cold-induced depolymerization, suggesting that they are functionally different as well. The composition and distribution of modified microtubules change as cells undergo the morphogenesis associated with polarization. Two-dimensionally polarized spreading cells have more detyrosinated microtubules that are oriented toward the leading edge, but three-dimensionally polarized cells have more acetylated microtubules that are oriented toward the apical domain. These data suggest that the transition from 2D polarity to 3D polarity involves both a reorganization of the microtubule cytoskeleton and a change in tubulin PTMs. However, in both 2D polarized and 3D polarized cells, the modified microtubules are oriented to support vectorial cargo transport to areas of high need.
微管翻译后修饰 (PTMs) 被认为为分子马达提供了导航线索，以将货物运送到空间分隔的亚细胞域，但这一过程的分子细节仍不清楚。在这里，我们表明在 Madin-Darby Canine Kidney (MDCK) 上皮细胞中，微管表达几种微管 PTMs。然而，这些修饰并不协调，细胞中有多种微管亚群，这些亚群由不同的 PTM 组合标记。此外，这些亚群对药物和冷诱导的解聚表现出不同的敏感性，表明它们在功能上也不同。随着细胞经历与极化相关的形态发生，修饰微管的组成和分布发生变化。二维极化扩展细胞具有更多的去酪氨酸化微管，这些微管朝向前沿定向，但三维极化细胞具有更多的乙酰化微管，这些微管朝向顶端域定向。这些数据表明，从 2D 极性到 3D 极性的转变既涉及微管细胞骨架的重新组织，也涉及微管 PTMs 的变化。然而，在二维极化和三维极化的细胞中，修饰的微管都被定向以支持向量货物运输到高需求区域。
