Alix (apotosis linked gene 2 interacting protein X) has been implicated in the biogenesis of the multivesicular bodies that mediate transport between early endosomes and late endosomes/lysosomes. However, its exact cellular function is unclear. Harald Stenmark and colleagues now propose that Alix helps to connect the cortical actin skeleton to endosomes (see ). The authors report that downregulation of Alix expression in HeLa cells by RNAi causes early and recycling endosomes to redistribute from a peripheral to a perinuclear location. Surprisingly, this redistribution does not affect transferrin recycling or the degradation of endocytosed epidermal growth factor receptors. Alix depletion does, however, cause an accumulation of unusual actin structures similar to those seen on depletion of HipR, a protein that facilitates the interaction between the cortical actin skeleton and the endocytic machinery. These and other results suggest that Alix also acts at this interface, although what it does there and how it connects with the actin cytoskeleton remain to be determined.
