THE DYNAMIC ORGANIZATION OF THE SECRETORY PATHWAY

The secretory pathway of eukaryotic cells consists of a number of dist inct 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 sor ting - proteins may reach the wrong compartment but are continually re trieved. A good example is the retrieval system for lumenal ER protein s. These proteins carry a specific sorting signal, typically the tetra peptide 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, includin g the coat proteins required for vesicle budding from the ER, those th at form retrograde vesicles on post-ER compartments, and integral memb rane proteins that target the vesicles to their correct destination, h ave been identified. The sorting events that occur can largely be unde rstood in terms of specific protein-protein interactions involving the se components. However, sorting of some membrane proteins, including t he vesicle targeting molecules, is influenced by their transmembrane d omains, and it is likely that segregation of these is dependent on the composition and biophysical properties of the lipid bilayer, which ve ry between compartments. The secretory pathway is thus a dynamic entit y, split into discrete organelles by the constant segregation and recy cling of lipids and proteins, processes that are ultimately driven by the mechanics of vesicle formation and fusion.