The posttranslational modification of tubulin undergoes a switch from detyrosination to acetylation as epithelial cells become polarized.
The posttranslational modification of tubulin undergoes a switch from detyrosination to acetylation as epithelial cells become polarized.
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DOI：
10.1091/mbc.e10-06-0519
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发表时间：
2011-04
影响因子：
3.3
通讯作者：
Ligon LA
中科院分区：
文献类型：
--
作者：
Quinones GB;Danowski BA;Devaraj A;Singh V;Ligon LA
极性导致微管蛋白修饰和微管组织的转变。在未极化的上皮细胞中，去酪氨酸微管指向扩展边缘，但在极化细胞中，乙酰化微管指向顶端域。在这两种情况下，修饰的微管都被定向为支持货物运输到高需求地区。微管蛋白翻译后修饰（PTM）已被建议提供导航线索的分子马达提供货物空间分离的亚细胞结构域，但这个过程的分子细节仍然不清楚。在这里，我们表明，在Madin-Darby犬肾（MDCK）上皮细胞，微管表达几个微管蛋白PTM。然而，这些修饰是不协调的，并且细胞具有由不同的PTM组合标记的多个微管亚群。此外，这些亚群对药物和冷诱导的解聚都表现出不同的敏感性，这表明它们在功能上也不同。修饰的微管的组成和分布随着细胞经历与极化相关的形态发生而改变。二维极化的伸展细胞有更多的脱酪氨酸微管，这些微管朝向前缘，但三维极化的细胞有更多的乙酰化微管，这些微管朝向顶端结构域。这些数据表明，从2D极性到3D极性的过渡涉及微管细胞骨架的重组和微管蛋白PTM的变化。然而，在2D极化和3D极化细胞中，修饰的微管被定向为支持向高需求区域的载体货物运输。
Polarity leads to a shift in tubulin modification and microtubule organization. In unpolarized epithelial cells, detyrosinated microtubules point to the spreading edge, but in polarized cells, acetylated microtubules point to the apical domain. In both cases the modified microtubules are oriented to support cargo transport to areas of high need. 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.