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Snapshot: Effector Proteins of Type III Secretion Systems Jorge E SnapShot: Effector Proteins of Type III Secretion Systems Jorge E. Galán Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA Effector Protein Bacteria Biochemical Function Cellular Target Phenotype SopE/SopE2 Salmonella enterica Guanine nucleotide exchange factor (GEF) Rho family GTPases Stimulation of actin reorganization and bacterial entry into nonphagocytic cells; nuclear responses SptP (N terminus)/YopE/ S. enterica/Yersinia GTPase-activating protein (GAP) Rho-family GTPases Recovery of the actin cytoskeleton after bacterial ExoS (N terminus) spp./Pseudomonas internalization (SptP); disruption of the actin cytoskeleton aeruginosa (YopE/ExoS) SipA S. enterica Actin nucleator Actin Stimulation of actin cytoskeleton reorganization and bacterial entry into nonphagocytic cells SopA S. enterica HECT-like ubiquitin ligase Unknown Promotes inflammation SopB/IpgB S. enterica/ Phosphoinositide and inositol phosphate Phosphoinositides Stimulation of actin cytoskeleton reorganization Shigella spp. phosphatase and inositol and macropinocytosis; bacterial internalization into phosphates nonphagocytic cells; modulation of vesicular trafficking SipC S. enterica Actin bundling Actin Modulation of actin cytoskeleton to promote bacterial internalization into host cells SifA S. enterica Recruits SKIP to the Salmonella-containing SKIP and kinesin Modulation of vesicular trafficking vacuole SseJ S. enterica Deacylase Unknown Unknown SseL S. enterica Ubiquitin protease Ubiquitin Macrophage killing SrfH S. enterica Unknown TRIP6 Promotes motility of infected cells SspH1 S. enterica Unknown PKN1 Inhibition of host inflammatory response? YopJ/AvrA/AvrBsT (and Yersinia spp./ Acetyl transferase/cysteine protease MAPKK and IKK family Disruption of MAP kinase and NF-κB signaling (YopJ); other family members) S. enterica members; SUMO? disruption of plant defense responses (AvrBsT) PipB2 S. enterica Recruitment of kinesin Kinesin Phagosome movement along microtubules? YopT/HopC1 (and other Yersinia spp./ Protease Rho-family GTPases Disruption of the actin cytoskeleton (YopT); modulates the family members) Pseudomonas syringae (YopT); PBS1 kinase jasmonic acid defense response in plants (AvrPphB) (AvrPphB) YopH/SptP (C terminus) Yersinia spp./S. enterica Protein tyrosine phosphatase Many Disruption of macrophage functions (YopH); disruption of MAP kinase signaling (SptP) YpkA Yersinia spp. Ser/Thr protein kinase Unknown Disruption of the actin cytoskeleton Tir Escherichia coli Intimin receptor; membrane recruitment of Nck; other signaling Actin nucleation at the plasma membrane; bacterial signaling and actin-nucleating machinery components? intimate attachment to host cells EspF/TccP2 E. coli WASP recruitment to plasma membrane/ WASP; Abcf2; SNX9 Promotes actin nucleation at the plasma membrane, intimate Abcf2 recruitment to mitochondria bacterial attachment, and mitochondrial death pathways IpgB1/IpgB2 (and other E. coli Proposed to mimic G protein function but Many Disruption of the actin cytoskeleton family members) lack nucleotide-binding or hydrolytic activity OspF (and other family E. coli Phosphothreonine lyase MAP kinases Disruption of inflammatory response members) Map E. coli Unknown EBP50/NHERF1 Promotes diarrhea OspG Shigella spp. Ser/Thr protein kinase Many ubiquitin- Disruption of NF-κB signaling conjugating enzymes VirA Shigella spp. Cysteine protease Tubulin Promotes intracellular movement IpaA Shigella spp. Mimics vinculin Actin cytoskeleton Promotes bacterial entry in nonphagocytic cells IpaH/SspH1 Shigella spp./S. enterica E3 ubiquitin ligase Unknown Disrupts inflammatory response? VopF Vibrio cholerae Actin nucleator; homolog of formin/spire Actin cytoskeleton Promotes intestinal colonization ExoS/ExoT (C terminus) P. aeruginosa ADP ribosyl transferase Many Disrupts actin cytoskeleton, tight junctions, and cytokinesis HopAB2/AvrPtoB (sev- P. syringae Ubiquitin-conjugating enzyme; E3 ligase Pto Ser/Thr kinase Inhibition of programmed cell death in plant cells eral family members) XopD (several family Xanthomonas campestris Cysteine protease SUMO Disruption of plant defense responses members) AvrRpt2 (several family P. syringae Protease RIN4 kinase Disruption of plant defense responses members) HopAO1/HopPtoD2 P. syringae Protein tyrosine phosphatase Unknown Suppression of programmed cell death in plant cells (several family members) HopU1 P. syringae ADP ribosyl transferase RNA-binding proteins Disruption of plant defense responses GALA family of proteins Ralstonia solanacearum F box proteins SKP1 plant homologs Promotes virulence in plants AvrBs2 X. campesteris pv. Glycerophosphoryl diester phophodies- Unknown Triggers defense response in plants vesicatoria terase AvrD1 P. syringae Syringolide synthase Unknown Triggers defense response in plants AvrBS3 Xanthomonas spp. Transcription factor Unknown Modulates plant gene expression 192 Cell 130, July 13, 2007 ©2007 Elsevier Inc. DOI 10.1016/j.cell.2007.06.042 See online version for legend, abbreviations, and references. SnapShot: Effector Proteins of Type III Secretion Systems Jorge E. Galán Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA Listed in this Table are type III secretion effector proteins whose function, biochemical activities, and/or putative eukaryotic cell targets have been reported. Type III protein secretion systems are specialized bacterial organelles that deliver bacterial proteins into eukaryotic cells. This organelle can be found in bacterial species that have evolved a very close functional interface with their hosts. These bacteria can be symbiotic or pathogenic for a number of organisms including humans, plants, insects, or nematodes. The bacterial proteins delivered into eukaryotic cells, collectively known as “effector proteins,” have the capacity to modulate a large variety of host cell functions including cytoskeleton dynamics, cell cycle, transcription, protein degradation, and vesicular trafficking. Abreviations SKIP: SifA and kinesin-interacting protein (Kiaa0842); ubiquitously expressed protein of unknown function TRIP6: Thyroid receptor-interacting protein 6 PKN1: Protein kinase N1; involved in innate immune responses IKK: IκB kinase; involved in innate immune responses by activating NF-κB PBS1: serine/threonine protein kinase required for plant defense response Nck: adaptor protein containing SH2 and SH3 domains; involved in signal transduction WASP: Wiskott-Aldrich syndrome protein; promotes actin nucleation Abcf2: a member of the ABC-transporter family of proteins of unknown function SNX9: Sortin nexin 9; involved in endocytosis EBP50/NHERF1/EBP50: Na+/H+ exchanger regulator factor 1/ezrin-radixin-moesin binding phosphoprotein 50; involved in the regulation of ion transporters and in the trafficking of many transmembrane molecules Pto: Plant serine/threonine kinase that confers resistance to Pseudomona syringae pv. tomato RIN4: RPM1-interacting protein 4 SKP1: S phase kinase-associated protein REFERENCES Abrahams, G., and Hense, L.M. (2006). Manipulating cellular transport and immune responses: Dynamic interactions between intracellular Salmonella enterica and its host cells. Cell. Microbiol. 8, 728–737. Alto, N., Shao, F., Lazar, C., Brost, R., Chua, G., Mattoo, S., McMahon, S., Ghosh, P., Hughes, T., Boone, C., and Dixon, J. (2006). Identification of a bacterial type III effector family with G protein mimicry functions. Cell 124, 133–145. Caron, E., Crepin, V., Simpson, N., Knutton, S., Garmendia, J., and Frankel, G. (2006). Subversion of actin dynamics by EPEC and EHEC. Curr. Opin. Microbiol. 9, 40–45. Galán, J.E. (2001). Salmonella interaction with host cells: Type III secretion at work. Annu. Rev. Cell Dev. Biol. 17, 53–86. Galán, J.E., and Wolf-Watz, H. (2006). Protein delivery into eukaryotic cells by type III secretion machines. Nature 444, 567–573. Grant, S., Fisher, E., Chang, J., Mole, B., and Dangl, J. (2006). Subterfuge and manipulation: Type III effector proteins of phytopathogenic bacteria. Annu. Rev. Microbiol. 60, 425–449. Izard, T., Tran Van Nhieu, G., and Bois, P. (2006). Shigella applies molecular mimicry to subvert vinculin and invade host cells. J. Cell Biol. 175, 465–475. Kim, D.W., Lenzen, G., Page, A.L., Legrain, P., Sansonetti, P.J., and Parsot, C. (2005). The Shigella flexneri effector OspG interferes with innate immune responses by targeting ubiquitin-conjugating enzymes. Proc. Natl. Acad. Sci. USA 102, 14046–14051. Mukherjee, S., Hao, Y., Orth, K., and Ozawa, R. (2007). A newly discovered post-translational modification–the acetylation of serine and threonine residues. Trends Biochem. Sci. 32, 210–216. Rohde, J., Breitkreutz, A., Chenal, A., Sansonetti, P., and Parsot, C. (2007). Type III secretion effectors of the IpaH family are E3 ubiquitin ligases. Cell Host Microbe 1, 77–83. Rytkonen, A., Poh, J., Garmendia, J., Boyle, C., Thompson, A., Liu, M., Freemont, P., Hinton, J.C., and Holden, D.W. (2007). SseL, a Salmonella deubiquitinase required for macrophage killing and virulence. Proc. Natl. Acad. Sci. USA 104, 3502–3507. Tam, V., Serruto, D., Dziejman, M., Brieher, W., and Mekalanos, J. (2007). A Type III secretion system in Vibrio cholerae translocates a formin/spire hybrid-like actin nucleator to promote intestinal colonization. Cell Host Microbe 1, 95–107. Viboud, G., and Bliska, J. (2005). Yersinia outer proteins: Role in modulation of host cell signaling responses and pathogenesis. Annu. Rev. Microbiol. 59, 69–89. Worley, M., Nieman, G., Geddes, K., and Heffron, F. (2006). Salmonella typhimurium disseminates within its host by manipulating the motility of infected cells. Proc. Natl. Acad. Sci. USA 103, 17915–17920. Yoshida, S., Handa, Y., Suzuki, T., Ogawa, M., Suzuki, M., Tamai, A., Abe, A., Katayama, E., and Sasakawa, C. (2006). Microtubule-severing activity of Shigella is pivotal for intercellular spreading. Science 314, 985–989. Zhang, Y., Higashide, W., McCormick, B., Chen, J., and Zhou, D. (2006). Inflammation-associated Salmonella SopA is a HECT-like E3 ubiquitin ligase. Mol. Microbiol. 62, 786–793. 192.e1 Cell 130, July 13, 2007 ©2007 Elsevier Inc. DOI 10.1016/j.cell.2007.06.042 .
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