Rho regulates membrane transport in the endocytic pathway to control plasma membrane specialization in oligodendroglial cells

Rho regulates membrane transport in the endocytic pathway to control plasma membrane specialization in oligodendroglial cells
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DOI:
10.1523/jneurosci.4926-06.2007
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发表时间:
2007-03-28
影响因子:
5.3
通讯作者:
Simons, Mikael
Simons, Mikael
中科院分区:
医学1区
文献类型:
--
作者:
Kippert, Angelika;Trajkovic, Katarina;Simons, Mikael

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少突胶质细胞的分化与质膜结构的巨大变化有关,最终形成髓鞘膜鞘。先前的研究结果提供了证据表明,内吞作用的调节可能代表了一种控制髓鞘膜生长的机制。未成熟的少突胶质细胞具有高速率的网格蛋白非依赖性内吞作用,用于将膜转运至晚期内体/溶酶体(LE/Ls)。在成熟并接收来自神经元的信号后,内吞作用减少,并触发膜从LE/Ls向质膜的转运。在这里,我们表明,Rho GTdR活性的变化是负责这两种模式的膜运输之间的切换。引人注目的是,Rho失活不仅减少了货物运输到LE/L,但也增加了LE/L囊泡的动力学。此外,我们提供的证据表明,Rho失活的结果,在凝聚质膜的极化方式。总之,我们的数据揭示了一个新的作用Rho:调节膜的流动,并促进细胞表面结构和极性的变化,在少突胶质细胞。我们认为Rho失活是触发少突胶质细胞质膜特化所必需的。
Differentiation of oligodendrocytes is associated with dramatic changes in plasma membrane structure, culminating in the formation of myelin membrane sheaths. Previous results have provided evidence that regulation of endocytosis may represent a mechanism to control myelin membrane growth. Immature oligodendrocytes have a high rate of clathrin-independent endocytosis for the transport of membrane to late endosomes/lysosomes (LE/Ls). After maturation and receiving signals from neurons, endocytosis is reduced and transport of membrane from LE/Ls to the plasma membrane is triggered. Here, we show that changes in Rho GTPase activity are responsible for switching between these two modes of membrane transport. Strikingly, Rho inactivation did not only reduce the transport of cargo to LE/L but also increased the dynamics of LE/L vesicles. Furthermore, we provide evidence that Rho inactivation results in the condensation of the plasma membrane in a polarized manner. In summary, our data reveal a novel role of Rho: to regulate the flow of membrane and to promote changes in cell surface structure and polarity in oligodendroglial cells. We suggest that Rho inactivation is required to trigger plasma membrane specialization in oligodendrocytes.