Fig. 1. Model for the role of Arf1-GTP in the generation of transport vesicles. The productive pathway has the essential elements of the classical model for Arf1-dependent membrane trafficking. GAP recruitment was introduced when the model was modified to account for GTP-hydrolysis-dependent sorting. (1) Activation of Arf1 through GTP exchange for GDP by guanine nucleotide exchange factors at the membrane. (2) Arf1-GTP recruits coat proteins to membrane sites of vesicle formation. (3) Coat proteins bind to and concentrate cargo. (4) Arf GAPs are recruited to membrane sites of vesicle formation through binding to coat proteins or cargo proteins. (5) If the right cargos are present, GAP activity is inhibited and coat complexes polymerize to deform membrane. (6) Coated vesicle detaches from the membrane. (7) GTP on Arf is hydrolyzed by Arf GAP. Arf-GDP and Arf GAP dissociate. (8) Coat proteins dissociate to leave vesicles competent for docking and fusion with acceptor membranes. The discard pathway represents a modification of the classical model that explains a requirement for GTP hydrolysis in cargo sorting. In the text, we also refer to this modification as the `sorting by GAP inhibition' model. In the absence of correct cargo, Arf-GTP and coat proteins are recruited as in steps 1 and 2 of the productive pathway. (3) Arf GAP is recruited. (4) Since there is no cargo to inhibit GAP activity, GTP on Arf is hydrolyzed and Arf-GDP and Arf GAP dissociate from membrane. (5) Coat proteins dissociate from membrane.