Mechanisms of clathrin-mediated endocytosis

Key Points Clathrin-coated endocytic vesicles are produced by a complex modular protein machinery that transiently assembles on the plasma membrane. This machinery selects and concentrates cargo molecules and shapes the membrane into a vesicle. Forces arising within the membrane during deformation counteract forces generated by the endocytic protein modules. Physical parameters such as membrane tension and rigidity control the dynamics of clathrin-mediated endocytosis. Many endocytic proteins bind phosphoinositides, which are critical for organizing the sequence of protein assembly throughout endocytosis. The endocytic machinery is evolutionarily ancient and highly conserved, but it has adapted to varying force requirements in different lineages. Clathrin-mediated endocytosis is the main mechanism for internalization of cell-surface molecules and surface-bound cargoes. Although the machineries that drive the formation of endocytic vesicle are intricate, an understanding of endocytosis is being unravelled at the molecular level. Clathrin-mediated endocytosis is a key process in vesicular trafficking that transports a wide range of cargo molecules from the cell surface to the interior. Clathrin-mediated endocytosis was first described over 5 decades ago. Since its discovery, over 50 proteins have been shown to be part of the molecular machinery that generates the clathrin-coated endocytic vesicles. These proteins and the different steps of the endocytic process that they mediate have been studied in detail. However, we still lack a good understanding of how all these different components work together in a highly coordinated manner to drive vesicle formation. Nevertheless, studies in recent years have provided several important insights into how endocytic vesicles are built, starting from initiation, cargo loading and the mechanisms governing membrane bending to membrane scission and the release of the vesicle into the cytoplasm.