Possible mechanisms of lateral segregation Three non-exclusive processes are proposed to explain rapid spatial partitioning of transmembrane cargo from Golgi resident protein. All rely on enzymatic or cooperative processes to quickly generate a region of high cargo concentration. (1) Golgi associated lipid-modifying enzymes [48–50] catalytically contribute to the generation of a region with distinct lipid composition, to which transmembrane cargo (or certain classes of cargo) preferentially partition. (2) A multimeric or multivalent cargo receptor binds to cargo, causing it to cluster in the plane of the membrane. Polyvalent binding mechanisms have been shown to induce domains on the plasma membrane which are large enough to visualize with fluorescence microscopy . Coöperative binding could very rapidly generate a region of high cargo concentration. A good candidate for a cargo receptor would be a lectin which only binds after specific glycosylation events are completed [52, 53]. (3) Cytosolic coat proteins interact with signals in the tail of certain classes of cargo, perhaps via an adaptor (∩, ). Polymerization of the coat would rapidly cluster cargo into a coated region of the Golgi; such a mechanism is consistent with the several types of coated membranes on Golgi stacks observed by EM [1, 28]. Here, coat proteins are shown interacting with cargo, which would be consistent with the lower mobility of cargo in Golgi membranes compared to resident protein, but different coat proteins could also interact with Golgi resident proteins to sequester them away from cargo. For simplicity of presentation, they are considered separately, but we envision that partitioning of resident protein from cargo is most likely achieved by these mechanisms acting in combination.