The early steps of endocytosis: From cargo selection to membrane deformation

Clathrin-mediated endocytosis mediates the internalization of signaling and nutrient receptors, ion channels and regulates the endocytic recycling of pre- and postsynaptic membrane proteins. During early stages endocytic adaptors recognize sorting signals within this diverse array of cargo proteins destined for internalization. Cargo sequestration is mechanistically coupled to membrane deformation, a process involving BAR domain proteins, resulting in the generation of endocytic intermediates that finally undergo dynamin-mediated fission. Here we summarize recent insights gathered from a combination of structural, biochemical, and cell biological studies that have revealed a remarkable complexity of the machinery for endocytic sorting and membrane deformation.