Review series: From uncertain beginnings: initiation mechanisms of clathrin-mediated endocytosis

Clathrin-mediated endocytosis is a central and well-studied trafficking process in eukaryotic cells. How this process is initiated is likely to be a critical point in regulating endocytic activity spatially and temporally, but the underlying mechanisms are poorly understood. During the early stages of endocytosis three components-adaptor and accessory proteins, cargo, and lipids-come together at the plasma membrane to begin the formation of clathrin-coated vesicles. Although different models have been proposed, there is still no clear picture of how these three components cooperate to initiate endocytosis, which may indicate that there is some flexibility underlying this important event.