During the creation of a COPI transport vesicle, GTP–ARF1, a member of the RAS superfamily, binds to the donor membrane and recruits the coatomer complex to it. The coatomer complex binds to the donor membrane, inducing the formation of the vesicle. Once the vesicle has been formed, there is a stimulation of the GTPase activity on the ARF1 molecule both by coatomer and the ARF1 GTPase-activating protein (GAP), resulting in the dissociation of ARF1 and coatomer from the vesicle. This exposes the targeting proteins that are responsible for the recognition of the acceptor compartment by the transport vesicle. Increasing evidence has accumulated for a model in which the cargo to be transported interacts specifically with the coat proteins involved in creating the vesicle, thereby incorporating that cargo into the vesicle. However, many transported cargo molecules as well as resident nontransported molecules, despite having different sorting signals, are able to compete for the same binding site on the coatomer complex. How then can two proteins competing for the same binding site on the coat protein result in the selective incorporation of only one of the molecules and the exclusion of the molecule to remain in the donor organelle? Jonathan Goldberg presents data in this paper that suggest a very provocative model for how two competing signals can be deciphered by the coat proteins and result in the selective incorporation of one protein over another 1 Goldberg J. Decoding of sorting signals by coatomer through a GTPase switch in the COPI coat complex. Cell. 2000; 100: 671-679 Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar .