ARF6 Interacts with JIP4 to Control a Motor Switch Mechanism Regulating Endosome Traffic in Cytokinesis
ARF6 Interacts with JIP4 to Control a Motor Switch Mechanism Regulating Endosome Traffic in Cytokinesis
复制标题
DOI：
10.1016/j.cub.2008.12.043
复制
发表时间：
2009-02-10
期刊：
影响因子：
9.2
通讯作者：
Chavrier, Philippe
中科院分区：
文献类型：
--
作者：
Montagnac, Guillaume;Sibarita, Jean-Baptiste;Chavrier, Philippe
背景资料：最近的工作强调了内吞膜循环到细胞间桥对于完成动物细胞胞质分裂的重要性。ADP-核糖基化因子6（ARF 6）定位于质膜和内体区室，调节胞质分裂期间内吞再循环至桥，是胞质分裂所必需的。在这里，我们报告了JNK相互作用蛋白JIP 3和JIP 4，两个高度相关的JNK信号传导模块的支架蛋白，也作为驱动蛋白1和动力蛋白复合物的结合伴侣，可以作为ARF 6的下游效应物。在体外，GTP-ARF 6与JIP 3和JIP 4的第二亮氨酸拉链结构域的结合干扰了JIPs与驱动蛋白-1的结合，而它有利于JIPs与动力蛋白复合物的相互作用。通过小干扰RNA和显性抑制方法进行蛋白质沉默，我们发现ARF 6、JIP 4、驱动蛋白-1和dynactin复合物控制着再循环内体进出细胞间桥的运输，并且是终止所必需的。我们的研究结果揭示了ARF 6作为相反方向的马达蛋白的调节开关的一种新功能，该马达蛋白控制胞吞囊泡在细胞内的运输。细胞间的桥梁机制所需的脱落。
Background: Recent work has highlighted the importance of the recycling of endocytic membranes to the intercellular bridge for completion of cytokinesis in animal cells. ADP-ribosylation factor 6 (ARF6), which localizes to the plasma membrane and endosomal compartments, regulates endocytic recycling to the bridge during cytokinesis and is required for abscission.Results: Here, we report that the JNK-interacting proteins JIP3 and JIP4, two highly related scaffolding proteins for JNK signaling modules, also acting as binding partners of kinesin-1 and dynactin complex, can function as downstream effectors of ARF6. In vitro, binding of GTP-ARF6 to the second leucine zipper domain of JIP3 and JIP4 interferes with JIPs' association with kinesin-1, whereas it favors JIPs' interaction with the dynactin complex. With protein silencing by small interfering RNA and dominant inhibition approaches, we show that ARF6, JIP4, kinesin-1, and the dynactin complex control the trafficking of recycling endosomes in and out of the intercellular bridge and are necessary for abscission.Conclusion: Our findings reveal a novel function for ARF6 as a regulatory switch for motor proteins of opposing direction that controls trafficking of endocytic vesicles within the intercellular bridge in a mechanism required for abscission.