PtdIns(4)P regulates retromer-motor interaction to facilitate dynein-cargo dissociation at the trans-Golgi network.

Publisher: Macmillan Magazines Ltd Country of Publication: England NLM ID: 100890575 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4679 (Electronic) Linking ISSN: 14657392 NLM ISO Abbreviation: Nat Cell Biol Subsets: MEDLINE

Original Publication: London : Macmillan Magazines Ltd., [1999-

Dyneins/*metabolism ; Golgi Apparatus/*metabolism ; Intracellular Membranes/*metabolism ; Microtubule-Associated Proteins/*metabolism ; Phosphatidylinositol Phosphates/*metabolism ; trans-Golgi Network/*physiology; Amino Acid Sequence ; Dynactin Complex ; HeLa Cells ; Humans ; Image Processing, Computer-Assisted ; Immunoprecipitation ; Kidney/cytology ; Kidney/metabolism ; Microscopy, Fluorescence ; Molecular Sequence Data ; Protein Transport ; Sequence Homology, Amino Acid ; Sorting Nexins/metabolism

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.

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0 (DCTN1 protein, human)
0 (Dynactin Complex)
0 (Microtubule-Associated Proteins)
0 (Phosphatidylinositol Phosphates)
0 (SNX1 protein, human)
0 (SNX6 protein, human)
0 (Sorting Nexins)
0 (phosphatidylinositol 4-phosphate)
EC 3.6.4.2 (Dyneins)

Date Created: 20130326 Date Completed: 20130523 Latest Revision: 20211021

20240829

10.1038/ncb2710

23524952