Arf-family GTPases play important roles in membrane trafficking. They act at multiple sites, recruiting various adaptor proteins and coat complexes to budding vesicles. Arfs interact with GTPase-activating proteins (Arf GAPs), which stimulate hydrolysis of bound GTP. Unlike the Arfs, there are many different types of Arf GAP; so these could help provide specificity. Paul Randazzo and co-workers have tested this hypothesis by analysing the functions of the related Arf GAPs AGAP1 and AGAP2 (). AGAP1 specifically interacts with the clathrin adaptor protein AP-3 and regulates its function on endosomes. The authors demonstrate that AGAP2, by contrast, interacts with the adaptor AP-1. They reveal that it colocalizes with AP-1, transferrin receptors and the GTPase Rab4 on recycling endosomes, which are different from the AP3-bearing endosomes. In addition, Randazzo and co-workers show that AGAP2 regulates the distribution of AP-1 and promotes recycling of transferrin receptors. Their findings indicate that AGAP1 and AGAP2 can functionally discriminate between AP-1 and AP-3 and thus control trafficking through different endosomal compartments. They therefore constitute strong evidence for the proposal that Arf GAPs are important specificity determinants in Arf-based membrane trafficking.
