Coated vesicle adaptors

Coated vesicle adaptors are ancient sorting machines found in all eukaryotes. We have discovered or co-discovered five distinct adaptor protein (AP) complexes, which localise to different membranes. There are genetic disorders caused by mutations in AP subunits, and APs can be hijacked by pathogens. But in spite of their importance, the AP complexes remain enigmatic, with many unanswered questions about what they actually do. Genetic studies have produced contradictory results, probably because of indirect effects on other pathways. We recently developed new approaches for investigating the role of AP-1 more directly, and showed that it facilitates retrograde traffic back to the late Golgi in HeLa cells. We now plan to use these approaches for two specific aims. First, we will analyse AP-1 function in differentiated mammalian cells, where it has been implicated in multiple pathways. Second, we will investigate the functions of all five complexes, not only in mammals but in multiple organisms, for a unified eukaryote-wide view. To explore the origins of the five complexes, we will investigate related proteins in our closest prokaryotic relatives. Together, these studies will provide new insights into the role of the AP complexes in health, in disease, and in our evolutionary history.