Spatial Regulation of Exocytosis: Lessons from Yeast

M any types of cells maintain specialized plasma membrane domains to which different subsets of secretory vesicles are targeted, enabling the cells’ performance of specific functions. The budding yeast Saccharomyces cerevisiae spatially and temporally regulates exocytosis, directing surface growth and secretion to different plasma membrane sites at different cell cycle stages (21). In very small buds, secretion occurs over the entire bud surface, but as the bud enlarges growth is directed to the bud tip. When the bud is two-thirds the size of the mother cell, secretion becomes isotropic over the entire bud surface. Late in the cell cycle, new material is inserted at the neck between mother and daughter cells, resulting in cytokinesis and septation. The accurate delivery of vesicles to sites of exocytosis requires both actin-dependent vesicle transport and actinindependent establishment of a vesicle-receiving station. The first step, polarized vesicle transport, also involves a rab family small GTPase and its nucleotide exchange protein. The next step, docking of secretory vesicles at specific sites, involves a large protein complex peripherally associated with the plasma membrane at these sites. The final step, vesicle fusion, involves the integral membrane soluble N -ethylmaleimide–sensitive factor (NSF) attachment protein receptor (SNARE) 1 proteins and their regulators (31). The target-SNAREs are distributed over the entire plasma membrane, not just at the regions of active exocytosis (7). Although the interaction of correctly paired vesicleand target-SNAREs is proposed to specify the correct membrane fusion reaction (35), the restriction of exocytosis to particular regions of the plasma membrane is accomplished at the vesicle docking stage. We will consider the roles of the cytoskeletal and secretory machinery in the establishment of a polarized secretory pathway.