Peter S. McPherson, Brigitte Ritter and Beverly Wendland
Eukaryotic cells use multiple pathways for the endocytic entry of proteins and lipids at the plasma membrane. To date, the best characterized pathway is clathrin-mediated endocytosis. This chapter presents an overview of the mechanisms of clathrin-mediated endocytosis and how it is regulated. We provide a mechanistic description of how a clathrin-coated vesicle (CCV) is formed, from the stages of initiation to scission to uncoating, as well as address important regulation by protein and lipid kinases and phosphatases. Endocytic events are initiated through the concerted action of the clathrin coat and adaptor proteins that select the transmembrane proteins (cargo) that will be carried into the cell in endocytic vesicles. Accessory proteins and the GTPase dynamin work together with forces provided by actin polymerization to complete the formation of the CCV. The ATPase chaperone Hsc70 and the protein auxilin promote CCV uncoating, a necessary step for the vesicle to fuse with endosomes. The synergistic convergence of powerful experimental strategies such as structural, biochemical and genomic approaches, in vitro assays, and real-time imaging in vivo, have combined to allow the new breakthroughs that are discussed.