An unmet actin requirement explains the mitotic inhibition of clathrin-mediated endocytosis
An unmet actin requirement explains the mitotic inhibition of clathrin-mediated endocytosis
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DOI：
10.1101/001701
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发表时间：
2014-01
期刊：
影响因子：
7.7
通讯作者：
S. Kaur;A. Fielding;Gisela Gassner;N. J. Carter;S. Royle
中科院分区：
文献类型：
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作者：
S. Kaur;A. Fielding;Gisela Gassner;N. J. Carter;S. Royle
网格蛋白介导的内吞作用（CME）是哺乳动物细胞中许多不同受体类型的主要内化途径。CME在有丝分裂早期被关闭，但这种抑制的机制尚不清楚。在这里，我们表明，有丝分裂关闭是由于未满足的要求肌动蛋白在CME。在有丝分裂细胞中，膜张力增加，这引起了对肌动蛋白细胞骨架的需求，以帮助CME机器克服增加的负荷。然而，肌动蛋白细胞骨架参与有丝分裂细胞中刚性皮质的形成，因此无法部署。我们证明，CME可以“重新启动”有丝分裂细胞，尽管高膜张力，通过允许肌动蛋白参与内吞作用。内吞蛋白的有丝分裂磷酸化在具有恢复的CME的有丝分裂细胞中维持，表明CME机制的直接磷酸化不能解释关闭。
Clathrin-mediated endocytosis (CME) is the major internalisation route for many different receptor types in mammalian cells. CME is shut down during early mitosis, but the mechanism of this inhibition is unclear. Here we show that the mitotic shutdown is due to an unmet requirement for actin in CME. In mitotic cells, membrane tension is increased and this invokes a requirement for the actin cytoskeleton to assist the CME machinery to overcome the increased load. However, the actin cytoskeleton is engaged in the formation of a rigid cortex in mitotic cells and is therefore unavailable for deployment. We demonstrate that CME can be “restarted” in mitotic cells despite high membrane tension, by allowing actin to engage in endocytosis. Mitotic phosphorylation of endocytic proteins is maintained in mitotic cells with restored CME, indicating that direct phosphorylation of the CME machinery does not account for shutdown.