SopE acts as an Rab5-specific nucleotide exchange factor and recruits non-prenylated Rab5 on Salmonella-containing phagosomes to promote fusion with early endosomes.

Rab-GTPase regulates the fusion between two specific vesicles. It is well documented that, for their biological function, Rab proteins need to be prenylated for attachment to the vesicle membrane. In contrast, we showed in the present investigation that SopE, a type III secretory protein of Salmonella, translocates onto Salmonella-containing phagosomes (LSP) and mediates the recruitment of non-prenylated Rab5 (Rab5:DeltaC4) on LSP in GTP form. Simultaneously, SopE present in infected cell cytosol acts as an Rab5-specific exchange factor and converts the inactive Rab-GDP to the GTP form. The non-prenylated Rab5 subsequently promoted efficient fusion of LSP with early endosomes. This is the first demonstration that a prenylation-deficient Rab protein retains biological activity and can promote vesicle fusion, if it is recruited on the membrane by some other method.