The Croonian Lecture 1999. Intracellular membrane traffic: getting proteins sorted

The secretory and endocytic pathways within higher cells consist of multipl e membrane-bound compartments, each with a characteristic composition, thro ugh which proteins move on their way to or from the cell surface. Sorting o f proteins within this system is achieved by their selective incorporation into budding vesicles and the specific fusion of these with an appropriate target membrane. Cytosolic coat proteins help to select vesicle contents, w hile fusion is mediated by membrane proteins termed SNAREs present in both vesicles and target membranes. SNAREs are not the sole determinants of targ et specificity but they lie at the heart of the fusion process. The complet e set of SNAREs is known in yeast, and analysis of their locations, interac tions and functions in vivo gives a comprehensive picture of the traffic ro utes and the ways in which organelles such as the Golgi apparatus are forme d. The principles of protein and lipid sorting revealed by this analysis ar e likely to apply to a wide variety of eukaryotic cells.