[Published in 'Research Highlights' a blog from Nature Cell Biology, February 1, 2013]
By Christina Karlsson Rosenthal – Planar cell polarity (PCP) co-organizes the polarity of individual epithelial cells and is critical in development, but exactly how PCP components such as Vangl2 are correctly distributed remains unclear. Schekman and colleagues demonstrate that Vangl2 is transported from the trans Golgi network (TGN) in a manner dependent on the small GTPase Arfrp1 and the clathrin adaptor AP-1 (eLife http://doi.org/j7c; 2013).
An siRNA screen of TGN-localized Arf proteins demonstrated that the loss of Arfrp1 resulted in defective exit of Vangl2 from the TGN. Clathrin and AP-1 vesicle coat proteins are involved in protein sorting at the Golgi, and the authors found that AP-1 preferentially binds to the GTP-bound form of Arfrp1. A known AP-binding basolateral sorting motif in Vangl2 was shown to mediate export of Vangl2 from the TGN and to directly interact with the μ1 subunit of AP-1. Furthermore, knockdown of AP-1 subunits caused Vangl2 to accumulate at the TGN. Experiments in which purified components were incubated with synthetic liposomes led the authors to propose that an interaction between Arfrp1–GTP and AP-1 recruits Vangl2 through its sorting motif, and this in turn stabilizes AP-1 membrane localization.