title: PtdIns(4)P regulates retromer-motor interaction to facilitate dynein-cargo dissociation at the trans-Golgi network.
abstract: 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.
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Niu
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Zhe
authors.initials: Z
authors.lastname: Sun
authors.forename: Zhi
authors.initials: Z
authors.lastname: Hong
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.forename: Demeng
authors.initials: D
authors.lastname: Sun
authors.forename: Yanrui
authors.initials: Y
authors.lastname: Yang
authors.forename: Changlin
authors.initials: C
authors.lastname: Tian
authors.forename: Weimin
authors.initials: W
authors.lastname: Gong
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007091:Image Processing, Computer-Assisted; D047468:Immunoprecipitation; D007425:Intracellular Membranes / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D021381:Protein Transport; D017386:Sequence Homology, Amino Acid; D058305:Sorting Nexins / Q000378:metabolism; D021601:trans-Golgi Network / Q000502:physiology*
chemical_list: C000606360:DCTN1 protein, human; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D018129:Phosphatidylinositol Phosphates; C513978:SNX1 protein, human; C431150:SNX6 protein, human; D058305:Sorting Nexins; C037178:phosphatidylinositol 4-phosphate; D004398:Dyneins