TOM1: a new PI5P effector at signalling endosomes

Lipids of the phosphoinositide family are important regulators of the endocytic pathway; they maintain the identity of different vesicular organelles and coordinate numerous trafficking processes. Among these lipids, phosphatidylinositol 5-monophosphate (PI5P), which is present in cell membranes at low concentrations, is the least studied. PI5P can be generated from PI(4,5)P₂ by the Shigella flexneri virulence factor IpgD, a PI(4,5)P₂ 4-phosphatase. Hélène Tronchère and colleagues have previously reported that an IpgD-mediated increase in PI5P results in alterations in the endocytic pathway, including blockade of bulk endocytosis and impaired maturation of early endosomes. In their study on page 815, the authors now undertake a proteomics-based approach to identify the PI5P effectors that are responsible for their previous observations. Comparing early endosomes from cells overexpressing IpgD with those from control cells led them to identify TOM1 [target of myb-1 (chicken)] as a factor that is enriched in PI5P-containing endosomes. Indeed, the authors report that the VHS domain of TOM1 can directly interact with PI5P. They then show that TOM1 is recruited to signalling endosomes by PI5P and that this recruitment is responsible for the perturbations of the endolysosomal pathway that they had previously observed. On the basis of these data, the authors propose that, owing to its role in early endocytosis, PI5P is a crucial coordinator of discrete trafficking steps and associated signalling pathways in the cell.