The secretory pathway of eukaryotic cells consists of a number of distinct 
membrane-bound compartments interconnected by vesicular traffic. Each 
compartment has a characteristic content of proteins and lipids, which must be 
maintained. This is achieved in most cases by active sorting-proteins may reach 
the wrong compartment but are continually retrieved. A good example is the 
retrieval system for lumenal ER proteins. These proteins carry a specific 
sorting signal, typically the tetrapeptide KDEL, which is bound by a receptor in 
the Golgi apparatus. The receptor-ligand complex, together with escaped ER 
membrane proteins, returns to the ER. Many of the components of vesicle traffic, 
including the coat proteins required for vesicle budding from the ER, those that 
form retrograde vesicles on post-ER compartments, and integral membrane proteins 
that target the vesicles to their correct destination, have been identified. The 
sorting events that occur can largely be understood in terms of specific 
protein-protein interactions involving these components. However, sorting of 
some membrane proteins, including the vesicle targeting molecules, is influenced 
by their transmembrane domains, and it is likely that segregation of these is 
dependent on the composition and biophysical properties of the lipid bilayer, 
which very between compartments. The secretory pathway is thus a dynamic entity, 
split into discrete organelles by the constant segregation and recycling of 
lipids and proteins, processes that are ultimately driven by the mechanics of 
vesicle formation and fusion.