String and knots: Tying clathrin to membranes

The transfer of macromolecules on the secretory and endocytic pathways occurs by the trafficking of membrane-bound vesicles between donor and acceptor compartments. These transport vesicles are classified according to the makeup of the protein coat that surrounds them during their genesis and early life. The best characterized class of coated vesicles are the clathrin-coated vesicles (CCVs). The formation of clathrin-coated transport vesicles requires, in general, three components. The first of these is the polyhedral clathrin coat, which serves as a scaffold with multiple points of attachment for the second component -- the adaptors. These link the protein cargo that is embedded in the membrane and/or specific phospholipid components of the membrane with the clathrin coat. The final component comprises a number of proteins that play accessory roles in vesicle genesis and subsequent steps including nucleation of coat formation, recruitment of cargo, membrane deformation, modification of phospholipid head-groups and the tethering and targeting of the completed vesicle. There are many proteins with varied structures that carry out these roles, and their functions are generally less well understood than either clathrin or the adaptors. For a review of clathrin-mediated endocytosis, see Brodsky et al.1.