Abstract:
Endocytosis was initially viewed as a mechanism of signal termination through the downregulation and degradation of surface receptors. However, more recent data argue that endosomal compartments contribute to intracellular signaling by transporting ligand-receptor complexes and affecting their activity inside the cell.
I will present our recent work on the role of endosomes in inducing inflammatory signaling from inside the cells. In particular, we found that impairing the function of some trafficking regulators, such as ESCRT subunits, induces inflammatory NF-κB signaling due to the aberrant accumulation of cytokine receptors on the outer membrane of endosomes. In turn, some other trafficking defects cause enclosure of cytokine receptors inside endosomes in intraluminal vesicles that prevents activation of signaling. Finally, I will describe how genetic defects in trafficking regulators occurring in tumorigenesis could be exploited therapeutically using the synthetic lethality concept