Differential activation and function of Rho GTPases during Salmonella-host cell interactions.
Salmonella enterica, the cause of food poisoning and typhoid fever, has evolved sophisticated mechanisms to modulate Rho family guanosine triphosphatases (GTPases) to mediate specific cellular responses such as actin remodeling, macropinocytosis, and nuclear responses. These responses are largely the result of the activity of a set of bacterial proteins (SopE, SopE2, and SopB) that, upon delivery into host cells via a type III secretion system, activate specific Rho family GTPases either directly (SopE and SopE2) or indirectly (SopB) through the stimulation of an endogenous exchange factor. We show that different Rho family GTPases play a distinct role in Salmonella-induced cellular responses. In addition, we report that SopB stimulates cellular responses by activating SH3-containing guanine nucleotide exchange factor (SGEF), an exchange factor for RhoG, which we found plays a central role in the actin cytoskeleton remodeling stimulated by Salmonella. These results reveal a remarkable level of complexity in the manipulation of Rho family GTPases by a bacterial pathogen.
Patel
Jayesh C
JC
Section of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, New Haven, CT 06536, USA.
Galán
Jorge E
JE
D000199:Actins / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism / Q000382:microbiology; D002522:Chlorocebus aethiops; D004789:Enzyme Activation; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology; D009154:Mutation; D034622:RNA Interference; D012480:Salmonella Infections / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000302:isolation & purification* / Q000472:pathogenicity; D014162:Transfection; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
C473930:ARHGEF26 protein, human; D000199:Actins; D001426:Bacterial Proteins; D020662:Guanine Nucleotide Exchange Factors; C103987:SopE protein, Salmonella; C436324:SopE2 protein, Salmonella typhimurium; C489224:SopB protein, Salmonella; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins