Subsequent steps in the secretory pathway involve vesicular transport between different compartments of the Golgi and from the Golgi to lysosomes or the plasma membrane. In each case, proteins within the lumen of one organelle are packaged into the budding transport vesicle and then released into the lumen of the recipient organelle following vesicle fusion. Membrane proteins and lipids are transported similarly, and it is noteworthy that their topological orientation is maintained as they travel from one membrane-enclosed organelle to another. For example, the domains of a protein exposed on the cytosolic side of the ER membrane will also be exposed on the cytosolic side of the Golgi and plasma membranes, whereas protein domains exposed on the lumenal side of the ER membrane will be exposed on the lumenal side of the Golgi and on the exterior of the cell (see Figure 9.10).
While most proteins travel from the ER to the Golgi, some proteins must be retained within the ER rather than proceeding along the secretory pathway. In particular, proteins that function within the ER (including BiP, signal peptidase, protein disulfide isomerase, and other enzymes discussed earlier) must be retained within that organelle. Export to the Golgi versus retention in the ER is thus the first branch point encountered by proteins being sorted to their correct destinations in the secretory pathway. Similar branch points arise at each subsequent stage of transport, such as retention in the Golgi versus export to lysosomes or the plasma membrane. In each case, specific localization signals target proteins to their correct intracellular destinations.