Manipulating endosomal systems: the molecular mechanisms of transport decisions and Salmonella-induced cancer

Endocytosis is a crucial mechanism for the cell to maintain homeostasis. By vesicular transport the cell is able to take up cargo from the cell surface, send molecules to the plasma membrane for excretion or to regulate positioning of internalized cargo in the cell. This thesis describes the regulation of transport complexes associated to these vesicles that determines their movement in the cell. Through recruitment of RAB7GAP the GTPase Rab7 can be removed from the vesicular membrane, allowing for transport mediated by another GTPase called Arl8b.The second part of this thesis focusses on the bacterium Salmonella which manipulates the endosomal system in order to create a niche that supports its own survival. By excretion of effector molecules Salmonella imodulates the membrane content of vesicles and thereby prevents its own lysosomal degradation. This allows Salmonella to create a Salmonella containing vesicle compartment that benefits its own survival in the host cell. This thesis describes how release of these effector molecules can support transformation of host cells. These results explain the strrong correlation between gallbladder cancer and chronic S. Typhi infections observed in patients from countries like India, where S. Typhi infections are still common.