Many epithelial tissues possess a pattern called planar cell polarity (PCP), defects in which will cause multiple developmental abnormality and diseases. PCP refers to the asymmetric protein distribution within cells. A group of conserved plasma-membrane localized signaling receptors, including the Frizzled proteins (Fzds) and Van Gogh like2 (Vangl2), regulate PCP by anchoring to the opposite side of the cells. Elaborate protein sorting machinery is utilized at the TGN to achieve robust and efficient transport processes. However, the molecular mechanisms of sorting of PCP proteins are not fully investigated. This study focuses on the PCP protein Vangl2 and the GTPase Arfrp1 to further investigate the spatial and functional roles of Arfrp1 in mediating protein sorting at the TGN. Arfrp1...[ Read more ]

Many epithelial tissues possess a pattern called planar cell polarity (PCP), defects in which will cause multiple developmental abnormality and diseases. PCP refers to the asymmetric protein distribution within cells. A group of conserved plasma-membrane localized signaling receptors, including the Frizzled proteins (Fzds) and Van Gogh like2 (Vangl2), regulate PCP by anchoring to the opposite side of the cells. Elaborate protein sorting machinery is utilized at the TGN to achieve robust and efficient transport processes. However, the molecular mechanisms of sorting of PCP proteins are not fully investigated. This study focuses on the PCP protein Vangl2 and the GTPase Arfrp1 to further investigate the spatial and functional roles of Arfrp1 in mediating protein sorting at the TGN. Arfrp1 is proposed to function upstream of Arl1 and Arl5 to mediate the retrograde tethering process to the TGN. Here, we hypothesize that Arfrp1, in addition to mediate vesicle tethering process, also mediates the sorting of Vangl2 and other specific groups of cargo protein at the TGN. We found that Arfrp1 directly regulates the TGN export of Vangl2. The post-Golgi trafficking of Vangl2 is inhibited by disrupting the functions of Arfrp1. Our results also suggest that Arfrp1 localizes at a distinct subdomain to mediate protein sorting at the TGN. Moreover, we identified several top hits co-enriched with Vangl2 into the transport vesicles, including EGFR. Our data indicate that Arfrp1 regulates TGN export of Vangl2 and other specific cargo proteins. To conclude, this study shed light on the mechanistic insight into Arfrp1-mediated protein sorting at the TGN.