Harnessing actin dynamics for clathrin-mediated endocytosis

Several lines of evidence have implicated the actin cytoskeleton in the internalization step of clathrin-mediated endocytosis in various organisms from yeast to mammals.Live-cell imaging studies have recently revealed a regular sequence of protein assembly events at endocytic sites. Actin and actin-cytoskeleton proteins are recruited to endocytic sites transiently during the budding of clathrin-coated endocytic vesicles.Functional assays indicate that actin might be required for steps such as the invagination of the plasma membrane, the constriction of the vesicle neck and the scission of the endocytic vesicle.Actin polymerization might provide the force for endocytic internalization. Proteins that link the growing actin-filament network to the endocytic coat might be used to harness the force of actin polymerization for vesicle budding.The actin-related protein-2/3 (Arp2/3) complex nucleates actin-filament polymerization at endocytic sites and is a key target of many regulatory proteins. In Saccharomyces cerevisiae, in which the most extensive functional studies have been carried out so far, the activity of the Arp2/3 complex at endocytic sites seems to be tightly controlled by both positive and negative regulators.Actin machinery that is similar to that used at endocytic sites is also used for the protrusion of lamellipodia. The same molecular machinery has therefore been adapted for different uses over the course of evolution.