The RACK1 Signaling Scaffold Protein Selectively Interacts with Yersinia pseudotuberculosis Virulence Function

Autor: Roland Nordfelth, Elin L. Isaksson, Mikael E. Sellin, Jonas Pettersson, Maria Fällman, Ekaterina Ivanova, Tomas Edgren, Hans Wolf-Watz, Sara E. Thorslund, Matthew S. Francis
Rok vydání: 2011
Předmět:
Bacterial Diseases
Scaffold protein
Non-Clinical Medicine
lcsh:Medicine
Pathogenesis
Yersinia
Biochemistry
Substrate Specificity
Mice
Cytosol
Molecular Cell Biology
Gram Negative
Yersinia pseudotuberculosis
lcsh:Science
Mice
Inbred BALB C
Multidisciplinary
biology
Effector
Biochemistry and Molecular Biology
Neoplasm Proteins
Bacterial Pathogens
Cell biology
Transport protein
Host-Pathogen Interaction
Protein Transport
Chemistry
Infectious Diseases
Medicine
Female
Porosity
Bacterial Outer Membrane Proteins
Protein Binding
Research Article
Molecular Sequence Data
Immunology
Virulence
Receptors
Cell Surface
Receptors for Activated C Kinase
Microbiology
Yersinia Pseudotuberculosis
GTP-binding protein regulators
Phagocytosis
GTP-Binding Proteins
Animals
Humans
Secretion
Amino Acid Sequence
Protein Interactions
Biology
Microbial Pathogens
lcsh:R
Proteins
biology.organism_classification
Yersinia Pseudotuberculosis Infection
lcsh:Q
Medicinal Chemistry
Biokemi och molekylärbiologi
HeLa Cells
Zdroj: PLoS ONE
PLoS ONE, Vol 6, Iss 2, p e16784 (2011)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0016784
Popis: Many Gram-negative bacteria use type III secretion systems to translocate effector proteins into host cells. These effectors interfere with cellular functions in a highly regulated manner resulting in effects that are beneficial for the bacteria. The pathogen Yersinia can resist phagocytosis by eukaryotic cells by translocating Yop effectors into the target cell cytoplasm. This is called antiphagocytosis, and constitutes an important virulence feature of this pathogen since it allows survival in immune cell rich lymphoid organs. We show here that the virulence protein YopK has a role in orchestrating effector translocation necessary for productive antiphagocytosis. We present data showing that YopK influences Yop effector translocation by modulating the ratio of the pore-forming proteins YopB and YopD in the target cell membrane. Further, we show that YopK that can interact with the translocators, is exposed inside target cells and binds to the eukaryotic signaling protein RACK1. This protein is engaged upon Y. pseudotuberculosis-mediated beta1-integrin activation and localizes to phagocytic cups. Cells with downregulated RACK1 levels are protected from antiphagocytosis. This resistance is not due to altered levels of translocated antiphagocytic effectors, and cells with reduced levels of RACK1 are still sensitive to the later occurring cytotoxic effect caused by the Yop effectors. Further, a yopK mutant unable to bind RACK1 shows an avirulent phenotype during mouse infection, suggesting that RACK1 targeting by YopK is a requirement for virulence. Together, our data imply that the local event of Yersinia-mediated antiphagocytosis involves a step where YopK, by binding RACK1, ensures an immediate specific spatial delivery of antiphagocytic effectors leading to productive inhibition of phagocytosis.
Databáze: OpenAIRE
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