PtdIns(4)P regulates retromer–motor interaction to facilitate dynein–cargo dissociation at the trans-Golgi network
    作者: Yang Niu,Cheng Zhang,Zhe Sun,Zhi Hong,Ke Li,Demeng Sun,Yanrui Yang,Changlin Tian,Weimin Gong & Jia-Jia Liu
    刊物名称: Nature Cell Biology
    DOI:
    联系作者:
    英文联系作者:
    卷:
    摘要:

    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 p150Glued 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.