Rab35 GTPase and OCRL phosphatase remodel lipids and F-actin for successful cytokinesis
Rab35 GTPase and OCRL phosphatase remodel lipids and F-actin for successful cytokinesis
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DOI：
10.1038/ncb2279
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发表时间：
2011-08-01
影响因子：
21.3
通讯作者：
Echard, Arnaud
中科院分区：
文献类型：
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作者：
Dambournet, Daphne;Machicoane, Mickael;Echard, Arnaud
脱落是细胞质分裂中最不为人所知的步骤。它包括在有丝分裂结束时连接姐妹细胞的细胞间桥的最终切割，并被认为涉及膜运输以及脂质和细胞骨架的重塑(1-6)。我们先前发现Rab35 GTP酶是快速循环内吞途径的调节因子，该途径对于后皱纹胞质分裂阶段是必不可少的(7)。在此，我们报道了在Lowe综合征患者(8，9)中突变的磷脂酰肌醇-4，5-二磷酸(PtdIns(4，5)P(2))5-磷酸酶OCRL是Rab35 GTP酶在胞质脱落中的效应。GTP结合(活性)的Rab35直接与OCRL相互作用，并控制其在细胞间桥的定位。Rab35或OCRL的缺失抑制了胞质的脱落，并与局部异常的PtdIns(4，5)P(2)和F-肌动蛋白在细胞间桥的积聚有关。这些分裂缺陷也在LOWE患者的细胞系中发现，可以通过添加低剂量的F-肌动蛋白解聚药物来纠正。我们的数据表明，PtdIns(4，5)P(2)的水解对于正常的胞质分裂脱落局部重塑细胞间桥中的F-肌动蛋白细胞骨架是重要的。他们还揭示了磷酸酶OCRL在细胞分裂中意想不到的作用，并为与洛维病相关的多效性表型提供了新的线索。
Abscission is the least understood step of cytokinesis. It consists of the final cut of the intercellular bridge connecting the sister cells at the end of mitosis, and is thought to involve membrane trafficking as well as lipid and cytoskeleton remodelling(1-6). We previously identified the Rab35 GTPase as a regulator of a fast recycling endocytic pathway that is essential for post-furrowing cytokinesis stages(7). Here, we report that the phosphatidylinositol-4,5-bisphosphate (PtdIns(4, 5)P(2)) 5-phosphatase OCRL, which is mutated in Lowe syndrome patients(8,9), is an effector of the Rab35 GTPase in cytokinesis abscission. GTP-bound (active) Rab35 directly interacts with OCRL and controls its localization at the intercellular bridge. Depletion of Rab35 or OCRL inhibits cytokinesis abscission and is associated with local abnormal PtdIns (4, 5)P(2) and F-actin accumulation in the intercellular bridge. These division defects are also found in cell lines derived from Lowe patients and can be corrected by the addition of low doses of F-actin depolymerization drugs. Our data demonstrate that PtdIns(4, 5)P(2) hydrolysis is important for normal cytokinesis abscission to locally remodel the F-actin cytoskeleton in the intercellular bridge. They also reveal an unexpected role for the phosphatase OCRL in cell division and shed new light on the pleiotropic phenotypes associated with Lowe disease.