Endophilin joins dynamin and amphiphysin in the league of endocytic proteins with lipid-deforming properties. All three proteins can act alone to deform membranes, and both amphiphysin and endophilin interact with dynamin, but the mode of action of the proteins remains obscure. Others had suggested that endophilin acts as an acyl transferase to modify the shape of inner leaflet phospholipids, and thus the membrane curvature. But Farsad et al. find that endophilin can tubulate membranes during an incubation that is either on ice or lacking the substrates for the relevant acyl transfer reaction.
The authors find that amphiphysin and endophilin share a short stretch of homology, essential for endophilin action, that may form an amphipathic helix. Such a helix could interact with both charged head groups and hydrophobic tails of membrane lipids, thus inserting into the membrane. The lipid-stimulated oligomerization of endophilin observed by the authors could then impose a new spacing on the membrane lipids of one leaflet of the membrane, thus inducing curvature and creating tubules. The different functions of endophilin, amphiphysin, and dynamin during this process are yet to be established. ▪