The trans Golgi network (TGN) is a distinct compartment at the exit site of the Golgl complex1 that appears as a network of tubules extending from the trans cisterna z. A major role of the TGN is the segregation of membrane and lumenal proteins Into different transport vesicles destined for endosomes, lysosomes, secretory granules and the plasma membrane1, 3. A paradigm for the molecular mechanism of sorting has come from studies of lysosomal enzyme biogenesis 4 and the endocytosis of extracellular ligands s. In both these well-studied examples the ligand to be sorted binds the extracytoplasmic domain of a receptor that can interact via its cytoplasmic domain with proteins of a coat structure involved in vesicle formation. By contrast, relatively little is known about the sorting of secretory proteins into vesicles destined for the cell surface, which is often referred to as a'default'pathway. However, several recent reports have indicated that this membrane trafficking pathway is highly regulated, involving heterotrimeric G proteins of the G s or Gi class 6-8. Furthermore, experiments designed to detect proteins cycling between the TGN and cell surface have confirmed that cycling proteins do exist 9, suggesting the possibility that'cargo'receptors might be involved.

A sorting receptor must be capable of interacting with coat components being assembled around a budding membrane so that the processes of content segregation and vesicle formation are efficiently coupled. This could be achieved by the activation of proteins that control the initiation of coat formation (possibly heterotrimeric G proteins, as has been suggested for the polymeric immunoglobulin receptorS), direct interactions with proteins of the coat (eg clathrin-adaptor complexes) or control of pinching-off of a vesicle (eg linking pinching-off to occupancy of sorting receptors). Candidates for the latter proofreading role might be found among the small GTP-binding proteins associated with organelles and transport vesicles as these can be charged with GTP enabling them to signal molecular events during membrane trafficking 11. A role has already been assigned to ARF (ADP ribosylation factor) proteins in the assembly of coatomer complexes onto transport vesicles involved in intracisternal transport in the Golgi complex 12. rab proteins 13, however, have not yet been assigned a definite role despite their specific intracellular localization 14, but are generally assumed to function in the targeting and fusion of transport vesicles is.