Temporal regulation of salmonella virulence effector function by proteasome-dependent protein degradation.
Salmonella enterica invasion of host cells requires the reversible activation of the Rho-family GTPases Cdc42 and Rac1 by the bacterially encoded GEF SopE and the GAP SptP, which exert their function at different times during infection and are delivered into host cells by a type III secretion system. We found that SopE and SptP are delivered in equivalent amounts early during infection. However, SopE is rapidly degraded through a proteosome-mediated pathway, while SptP exhibits much slower degradation kinetics. The half-lives of these effector proteins are determined by their secretion and translocation domains. Chimeric protein analysis indicated that delivery of SptP into host cells by the SopE secretion and translocation domain drastically shortened its half-life. Conversely, delivery of SopE by the SptP secretion and translocation signals significantly increased its half-life, resulting in persistent actin cytoskeleton rearrangements. This regulatory mechanism constitutes a remarkable example of a pathogen's adaptation to modulate cellular functions.
Kubori
Tomoko
T
Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
Galán
Jorge E
JE
D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D019556:COS Cells; D002455:Cell Division; D002522:Chlorocebus aethiops; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006207:Half-Life; D006790:Host-Parasite Interactions; D018715:Microscopy, Video; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism*; D019779:Salmonella enterica / Q000378:metabolism* / Q000472:pathogenicity*
D001426:Bacterial Proteins; D009097:Multienzyme Complexes; C103987:SopE protein, Salmonella; D017027:Protein Tyrosine Phosphatases; C439890:sptP protein, Salmonella typhimurium; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex