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Eukaryotic cells have an elaborate network of organelles, many of which are in constant and bidirecrional communication through a flow of small transport vesicles. For each organelle a specific mechanism exists to capture and package certain proteins and lipids that are destined for transport to a receiving compartment. In return, the receiving compartment accepts proteins that are meant to remain, or to be passed to another station, and then retrieves for recycling other proteins that belong in the donor organelle. Among the recycled proteins are structural components of the traffic pathway that must be used repeatedly to sustain transport. The most remarkable feature of this process is that selectivity is achieved in spite of the fluid nature of the membrane. In the absence of specific mechanisms to recognize and sequester proteins destined for transport and retrieval, communicating organelles would quickly lose their identity, succumbing to the lateral diffusional mobility of membrane proteins embedded within the bilayer. The evidence that we summarize in this review suggests that membrane identity is maintained by the selective capture into coated vesicles of proteins destined for transport.
Three Paradigms of Vesicle Bud Formation
Three models have contributed to our understanding of the mechanism of vesicle budding. The first is fashioned on the example of enveloped viruses that bud from the cell surface or into an intracellular compartment (1). In this example, a cytoplasmic nucleoprotein particle adheres to a virally encoded membrane or peripheral protein and deforms the membrane, clustering viral and possibly specific cellular proteins into the forming capsid. A cellular and topologically inverse analog to this could be cargo proteins that form a particle in the lumen of an organelle and recruit membrane proteins to bud a specific vesicle into the cytoplasm. The formation of a regulated secretory granule is thought to depend on the production of its contents, though it is not known if the cargo dictates the sorting process (2). This model probably does not apply to most incracellular traffic. Endocytosis and constitutive transport early in the secretory pathway do not require the presence of cargo molecules (3).
The second model of budding involves a consideration of the lateral and transverse organization of lipids within a membrane. Sheetz and Singer in their membrane bilayer couple hypothesis suggested...