Cytotoxic necrotizing factor-Y boosts Yersinia effector translocation by activating Rac protein
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Cytotoxic necrotizing factor-Y boosts Yersinia effector translocation by activating Rac protein. / Wolters, Manuel; Boyle, Colleen Erin; Lardong, Kerstin; Trülzsch, Konrad; Steffen, Anika; Rottner, Klemens; Ruckdeschel, Klaus; Aepfelbacher, Martin.
In: J BIOL CHEM, Vol. 288, No. 32, 09.08.2013, p. 23543-53.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Cytotoxic necrotizing factor-Y boosts Yersinia effector translocation by activating Rac protein
AU - Wolters, Manuel
AU - Boyle, Colleen Erin
AU - Lardong, Kerstin
AU - Trülzsch, Konrad
AU - Steffen, Anika
AU - Rottner, Klemens
AU - Ruckdeschel, Klaus
AU - Aepfelbacher, Martin
PY - 2013/8/9
Y1 - 2013/8/9
N2 - Pathogenic Yersinia spp. translocate the effectors YopT, YopE, and YopO/YpkA into target cells to inactivate Rho family GTP-binding proteins and block immune responses. Some Yersinia spp. also secrete the Rho protein activator cytotoxic necrotizing factor-Y (CNF-Y), but it has been unclear how the bacteria may benefit from Rho protein activation. We show here that CNF-Y increases Yop translocation in Yersinia enterocolitica-infected cells up to 5-fold. CNF-Y strongly activated RhoA and also delayed in time Rac1 and Cdc42, but when individually expressed, constitutively active mutants of Rac1, but not of RhoA, increased Yop translocation. Consistently, knock-out or knockdown of Rac1 but not of RhoA, -B, or -C inhibited Yersinia effector translocation in CNF-Y-treated and control cells. Activation or knockdown of Cdc42 also affected Yop translocation but much less efficiently than Rac. The increase in Yop translocation induced by CNF-Y was essentially independent of the presence of YopE, YopT, or YopO in the infecting Yersinia strain, indicating that none of the Yops reported to inhibit translocation could reverse the CNF-Y effect. In summary, the CNF-Y activity of Yersinia strongly enhances Yop translocation through activation of Rac.
AB - Pathogenic Yersinia spp. translocate the effectors YopT, YopE, and YopO/YpkA into target cells to inactivate Rho family GTP-binding proteins and block immune responses. Some Yersinia spp. also secrete the Rho protein activator cytotoxic necrotizing factor-Y (CNF-Y), but it has been unclear how the bacteria may benefit from Rho protein activation. We show here that CNF-Y increases Yop translocation in Yersinia enterocolitica-infected cells up to 5-fold. CNF-Y strongly activated RhoA and also delayed in time Rac1 and Cdc42, but when individually expressed, constitutively active mutants of Rac1, but not of RhoA, increased Yop translocation. Consistently, knock-out or knockdown of Rac1 but not of RhoA, -B, or -C inhibited Yersinia effector translocation in CNF-Y-treated and control cells. Activation or knockdown of Cdc42 also affected Yop translocation but much less efficiently than Rac. The increase in Yop translocation induced by CNF-Y was essentially independent of the presence of YopE, YopT, or YopO in the infecting Yersinia strain, indicating that none of the Yops reported to inhibit translocation could reverse the CNF-Y effect. In summary, the CNF-Y activity of Yersinia strongly enhances Yop translocation through activation of Rac.
KW - Animals
KW - Bacterial Outer Membrane Proteins
KW - Bacterial Toxins
KW - HeLa Cells
KW - Humans
KW - Mice
KW - Mice, Knockout
KW - Neuropeptides
KW - Protein Transport
KW - Yersinia Infections
KW - Yersinia enterocolitica
KW - cdc42 GTP-Binding Protein
KW - rac1 GTP-Binding Protein
KW - ras Proteins
KW - rho GTP-Binding Proteins
KW - rhoA GTP-Binding Protein
KW - rhoB GTP-Binding Protein
U2 - 10.1074/jbc.M112.448662
DO - 10.1074/jbc.M112.448662
M3 - SCORING: Journal article
C2 - 23803609
VL - 288
SP - 23543
EP - 23553
JO - J BIOL CHEM
JF - J BIOL CHEM
SN - 0021-9258
IS - 32
ER -