ARF-family GTPases function as regulators of multiple membrane trafficking processes in all eukaryotic cells. Six ARF proteins have been identified in humans, all of which contain a myristoyl residue, attached to their aminoterminal glycine by an amide bond. In their active, guanosine triphosphatebound (GTP-bound) state ARFs associate with membranes and trigger the recruitment of cytosolic proteins to the membrane. The switch to the GTPbound tate is under the control of a family of ARF-directed guanine-nucleotideexchange proteins containing a Sec7-homology domain (for reviewseeref. 1 ). The subsequent deactivation of ARFs and their dissociation from membranes depends on the hydrolysis of bound GTP. However, ARF proteins are devoid of intrinsic GTPase activity, and GTP hydrolysis depends on the action of GTPase-activating proteins (GAPs). ARF GAPs are a family of proteins which contain a conserved GAP domain of approx 130 amino acids with a unique Cys4 zinc-finger motif near their amino-terminal part (2 –9 ). Different ARF GAPs display a limited specificity to various ARF proteins in vitro, whereas additional specificity may be provided by targeting to distinct cellular compartments through variable domains that are present on various GAP molecules (10 –12 ).
