PtdIns(4)P regulates retromer-motor interaction to facilitate dynein-cargo dissociation at the trans-Golgi network
PtdIns(4)P regulates retromer-motor interaction to facilitate dynein-cargo dissociation at the trans-Golgi network
复制标题
PtdIns(4)P 调节逆转录体-运动相互作用以促进跨高尔基体网络处的动力蛋白-货物解离
DOI：
10.1038/ncb2710
复制
发表时间：
2013-04-01
影响因子：
21.3
通讯作者：
Liu, Jia-Jia
中科院分区：
文献类型：
--
作者：
Niu, Yang;Zhang, Cheng;Liu, Jia-Jia
逆行运动动力蛋白-动力蛋白在其最终目的地卸载其货物的分子机制仍有待阐明。在这项研究中，我们已经调查了在trans-Golgi网络（TGN）的逆转录酶相关货物的释放的监管机制。我们报道了一种富含高尔基体的磷脂酰肌醇-4-磷酸（PtdIns（4）P）负调控动力蛋白-动力肌动蛋白的p150（Glued）亚基与逆转录组分SNX 6之间的蛋白质-蛋白质相互作用。我们发现PtdIns（4）P特异性地促进TGN上逆转录酶介导的膜货物从运动中解离，并揭示了PtdIns（4）P在逆行囊泡运输到TGN膜的空间控制中的重要功能。PtdIns（4）P还通过调节其与动力蛋白的相互作用来调节SNX 4介导的囊泡向内吞再循环区室的逆行运输。这些结果建立了细胞器特异性磷酸肌醇调节马达-货物相互作用作为分子马达在靶膜上释放货物的机制。
The molecular mechanisms for the retrograde motor dynein-dynactin to unload its cargoes at their final destination remain to be elucidated. In this study, we have investigated the regulatory mechanism underlying release of retromer-associated cargoes at the trans-Golgi network (TGN). We report that phosphotidylinositol-4-phosphate (PtdIns(4)P), a Golgi-enriched phosphoinositide, negatively regulates the protein-protein interaction between the p150(Glued) subunit of dynein-dynactin and the retromer component SNX6. We show that PtdIns(4)P specifically facilitates dissociation of retromer-mediated membranous cargoes from the motor at the TGN and uncover an important function for PtdIns(4)P in the spatial control of retrograde vesicular trafficking to the TGN membrane. PtdIns(4)P also regulates SNX4-mediated retrograde vesicular trafficking to the endocytic recycling compartment by modulating its interaction with dynein. These results establish organelle-specific phosphoinositide regulation of motor-cargo interaction as a mechanism for cargo release by molecular motors at target membrane.