Models for the functions of Arf GAPs.

Arf GAPs (ADP-ribosylation factor GTPase-activating proteins) are essential components of Arf (ADP-ribosylation factor) signaling pathways. Arf GAPs stimulate the hydrolysis of GTP to GDP to transition Arf from the active, GTP bound, state to the inactive, GDP bound, state. Based on this activity, Arf GAPs were initially proposed to function primarily or exclusively as terminators of Arf signaling. Further studies of Arf GAPs have revealed that they also function as effectors of Arf signaling in at least a few steps or processes in which Arfs are not directly involved. In this review we discuss the non-canonical functions of Arf GAPs and address several key questions in the field, including: whether (1) Arf GAPs are terminators or effectors of Arf signaling, (2) Arf GAPs positively or negatively regulate COPI assembly, (3) Arf GAPs are involved in vesicle fission, and (4) Arf GAPs regulate vesicle uncoating.