Navarro Negredo Paloma, Edgar James R, Manna Paul T, Antrobus Robin, Robinson Margaret S
Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, UK.
Nat Commun. 2018 Feb 9;9(1):596. doi: 10.1038/s41467-018-02919-4.
Vesicluar transport of proteins from endosomes to the trans-Golgi network (TGN) is an essential cellular pathway, but much of its machinery is still unknown. A screen for genes involved in endosome-to-TGN trafficking produced two hits, the adaptor protein-1 (AP-1 complex), which facilitates vesicle budding, and WDR11. Here we demonstrate that WDR11 forms a stable complex with two other proteins, which localises to the TGN region and does not appear to be associated with AP-1, suggesting it may act downstream from budding. In a vesicle tethering assay, capture of vesicles by golgin-245 was substantially reduced in WDR11-knockout cells. Moreover, structured illumination microscopy and relocation assays indicate that the WDR11 complex is initially recruited onto vesicles rather than the TGN, where it may in turn recruit the golgin binding partner TBC1D23. We propose that the complex acts together with TBC1D23 to facilitate the golgin-mediated capture of vesicles that were generated using AP-1.
蛋白质从内体到反式高尔基体网络（TGN）的囊泡运输是一条重要的细胞途径，但其许多机制仍不清楚。一项针对参与内体到TGN运输的基因的筛选发现了两个命中基因，即促进囊泡出芽的衔接蛋白1（AP-1复合物）和WDR11。在此，我们证明WDR11与另外两种蛋白质形成稳定复合物，该复合物定位于TGN区域，且似乎不与AP-1相关，这表明它可能在出芽下游起作用。在囊泡拴系试验中，WDR11基因敲除细胞中高尔基体蛋白245对囊泡的捕获显著减少。此外，结构照明显微镜和重新定位试验表明，WDR11复合物最初被招募到囊泡上，而不是TGN上，在TGN上它可能反过来招募高尔基体结合伴侣TBC1D23。我们提出，该复合物与TBC1D23共同作用，促进高尔基体介导的对使用AP-1产生的囊泡的捕获。
