Effectors of the type III secretion systems (T3SS) are key elements in the interaction between many Gram-negative pathogens and their hosts. SlrP is an effector that is translocated into the eukaryotic host cell through the two virulence-associated T3SS of Salmonella enterica. We found previously that this effector is an E3 ubiquitin ligase for mammalian thioredoxin. Here, we identified ERdj3, an endoplasmic reticulum lumenal chaperone of the Hsp40/DnaJ family, as a new target for SlrP. Experiments with truncated forms of ERdj3 showed that domain II was essential for the interaction with SlrP. Confocal microscopy and subcellular fractionation demonstrated that, in transfected HeLa cells, SlrP was partially located in the endoplasmic reticulum. The presence of SlrP interfered with the binding of ERdj3 to a denatured substrate. Taken together, these data suggest that the role of SlrP in the interaction between Salmonella and the host cell is exerted through the modulation of the function of two independent targets: thioredoxin in the cytosol, and ERdj3 in the endoplasmic reticulum.
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Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USAUniv Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA
Tsai, Chi-Lin
Burkinshaw, Brianne J.
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Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V5Z 1M9, Canada
Univ British Columbia, Ctr Blood Res, Vancouver, BC V5Z 1M9, CanadaUniv Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA
Burkinshaw, Brianne J.
Strynadka, Natalie C. J.
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Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V5Z 1M9, Canada
Univ British Columbia, Ctr Blood Res, Vancouver, BC V5Z 1M9, CanadaUniv Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA
Strynadka, Natalie C. J.
Tainer, John A.
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Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USAUniv Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA
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Univ Rochester, Dept Med, Rochester, NY 14627 USAUniv Rochester, Dept Med, Rochester, NY 14627 USA
Lu, Rong
Wu, Shaoping
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Univ Rochester, Dept Med, Rochester, NY 14627 USAUniv Rochester, Dept Med, Rochester, NY 14627 USA
Wu, Shaoping
Liu, Xingyin
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Univ Rochester, Dept Med, Rochester, NY 14627 USAUniv Rochester, Dept Med, Rochester, NY 14627 USA
Liu, Xingyin
Xia, Yinglin
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Univ Rochester, Dept Biostat & Computat Biol, Rochester, NY USAUniv Rochester, Dept Med, Rochester, NY 14627 USA
Xia, Yinglin
Zhang, Yong-Guo
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Univ Rochester, Dept Med, Rochester, NY 14627 USAUniv Rochester, Dept Med, Rochester, NY 14627 USA
Zhang, Yong-Guo
Sun, Jun
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Univ Rochester, Dept Med, Rochester, NY 14627 USA
Univ Rochester, Dept Microbiol & Immunol, Rochester, NY USA
Univ Rochester, Wilmot Canc Ctr, Rochester, NY USAUniv Rochester, Dept Med, Rochester, NY 14627 USA