Endophilin marks and controls a clathrin-independent endocytic pathway

Cells internalize nutrients and turnover membrane components through the process of endocytosis, which in most cases involves the protein clathrin. Endophilin has been thought to be a component of clathrin-mediated endocytosis, but two studies published in this issue of Nature show that this protein mediates a fast-acting, clathrin-independent form of endocytosis which involves formation of tubular vesicles. Emmanuel Boucrot et al. report that this pathway is triggered by binding of ligands to cargo receptors, and requires the proteins dynamin and actin. Endophilin-mediated endocytosis also seems to have distinct cellular homes, occurring at the leading edges of cells where the lipid PtdIns(3,4)P2 ensures endophilin engagement. This form of endocytosis is shown to mediate the uptake of several physiological and disease-relevant receptors including G-protein-coupled receptors and receptor tyrosine kinases. In the second paper, Henri-Franois Renard et al. provide evidence that bacterial toxins take advantage of the same pathway to enter cells, and also find that endophilin-A2 acts together with dynamin and actin.