The C-terminal Eps15 homology domain (EHD) proteins have recently been described to regulate endosomal membrane trafficking, in particular cargo recycling from endosomes. In humans, there are four EHD proteins, whereas other organisms only have a single homologue. In this study (p. ), François Letourneur and co-workers characterise the single EHD of Dictystelium discoideum. First, they report that Dictyostelium EHD binds to phosphatidylinositol 3-phosphate (PI3P) and localises to endosomal compartments, where this lipid is enriched, as well as to phagosomes. By performing a two-hydrid screen using the EHD as bait, the authors then show that the EHD interacts with Dynamin A (DymA). EHD and DymA associate with endomembranes independently from each other; however, they are simultaneously recruited to phagosomes and released from the membranes during phagosome maturation. Interestingly, deletion experiments suggest that EHD and DymA have non-redundant, independent functions in phagosome maturation. In contrast to DymA, which is known to control early stages of phagosome maturation, EHD is likely to regulate several key steps in the process. Furthermore, deletion of ehd results in increased endosome tubulation, pointing to a role for Dictyostelium EHD in tubule scission, as has been suggested for mammalian EHD proteins. Thus, this study presents the first evidence for a role of EHD proteins at phagosomes, but further work is needed to decipher the exact underlying molecular mechanisms.
