The series of organelles through which proteins pass on their way to reach the cell surface is known as the secretory vesicles. This is not to say only proteins that will be released into extracellular space follow this pathway – proteins destined for many compartments within the cell follow this route, in whole or part. During or after synthesis, proteins destined for transport to the cell surface are translocated into the lumen of the ER or its membrane. They then are incorporated into vesicles at ER exit sites (ERES) and transported to the dynamic cluster of tubular and vesicular compartments known as the ER-Golgi intermediate compartment (ERGIC) before continuing on to the Golgi. The Golgi in mammalian cells appears as stacks of flat compartments known as cisternae, while in S. cerevisiae the “stack” formation is less apparent and there is no ERGIC compartment. The termini of the Golgi are named from the point of view of the ER: new secretory cargo enter at the cis-Golgi and eventually reach the trans-Golgi. Whether proteins move through the stacks or the stacks mature from cis to trans has been a subject of debate, but either way, proteins traversing the secretory pathway eventually reach a sorting station at the end of the Golgi known as the trans-Golgi network (TGN).
A subset of the proteins that reach the TGN are sorted into secretory vesicles, and carried to the plasma membrane. Secretory vesicles deliver integral membrane proteins to the PM, and release soluble materials within the vesicle to the outside of the cell. Other proteins that reach the TGN are sorted into vesicles bound for compartments within the endosomal system. Yet others are directed back into the Golgi. Even within the population of secretory vesicles destined for the PM, there have been two varieties identified in yeast, each of which carries a different subset of secretory cargo. In mammalian cells there is additional complexity since many cell types are polarized. Different vesicles are formed to transport proteins to the apical or basolateral domains of cells, and the detailed mechanisms can vary between cell types. In yeast, polarization of secretion is much simpler: cells reorient their cytoskeleton to direct secretion toward the tip of new buds, and toward the mother-bud neck just before cytokinesis.