The secretory pathway from history to the state of the art

Maintenance of the structural and functional organization of a eucaryotic cell requires the correct targeting of proteins and lipids to their destinations. This is achieved by the delivery of newly synthesized material along the secretory pathway on one hand and by the retrieval of membranes on the other hand. Various models have been suggested over the years to explain traffic flow within the secretory pathway. The only two models that are under discussion to date are the "vesicular model" and the "cisternal maturation model". A wealth of information from various experimental approaches, strongly supports the vesicular model as the general mode of intracellular transport. Three major types of protein-coated transport vesicles are characterized in molecular detail, and have been attributed to various steps of the secretory pathway: COPII-coated vesicles allow exit from the endoplasmic reticulum (ER), COPI-coated vesicles carry proteins within the early secretory pathway, i.e. between ER and Golgi apparatus, and clathrin-coated vesicles mediate transport from the trans-Golgi network (TGN). In this review we will give an overview of the route of a protein along the secretory pathway and summarize the progress that was made within the last decades in the characterization of distinct intracellular transport steps. We will discuss the current models for the formation and fusion of vesicular carriers with a major focus on the mechanism underlying budding of a COPI-coated vesicle.