Our research interests are focused on endocytic mechanisms, and on protein trafficking along the endocytic pathways. We are particularly interested by a protein named Itch, an enzymes capable of attaching ubiquitin to other proteins. This process called ubiquitination can have many consequences, but in endocytosis it is generally used to tag the proteins to be internalized, or to mediate additional protein-protein interactions when it targets endocytic proteins themselves.

We have found that Itch is localized inside cells to the trans-Golgi network and endosomes. This distribution could allow Itch to interact with proteins coming from the plasma membrane after endocytosis, and to potentially modify them. To address this hypothesis, we examine the epidermal growth factor receptor (EGFR), a well studied plasma membrane protein that is readily endocytosed following activation. By modifying Itch expression level, or using Itch mutants designed in our laboratory, we are examining the importance of Itch mediated activity in endosomal protein traffic regulation.

Beyond the fundamental importance of this work toward a global understanding of cellular function, our work could reveal new target mechanisms to control tyrosine kinase receptors like EGFR, whose activity is often abnormal in tumorigenic cells.

Intracellular localization of the Itch protein (green fluorescence) at the Golgi (G) and endosomes (e). Endosomes are labeled by endocytic uptake of fluorescent EGF (red fluorescence). The yellow color indicates overlapping of both signals. (n), nucleus).