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The Campylobacter jejuni CiaD effector co-opts the host cell protein IQGAP1 to promote cell entry

Journal Article · · Nature Communications
Campylobacter jejuni is a foodborne pathogen that binds to and invades the epithelial cells lining the human intestinal tract. Maximal invasion of host cells by C. jejuni requires cell binding as well as delivery of the Cia proteins (Campylobacter invasion antigens) to the host cell cytosol via the flagellum. Here, we show that CiaD binds to the host cell protein IQGAP1 (a Ras GTPase-activating-like protein), thus displacing RacGAP1 from the IQGAP1 complex. This, in turn, leads to the unconstrained activity of the small GTPase Rac1, which is known to have roles in actin reorganization and internalization of C. jejuni. Our results represent the identification of a host cell protein targeted by a flagellar secreted effector protein and demonstrate that C. jejuni-stimulated Rac signaling is dependent on IQGAP1.
Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
Grant/Contract Number:
AC05-76RL01830
OSTI ID:
1781820
Report Number(s):
PNNL-SA--152634
Journal Information:
Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 12; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

References (79)

Structure and evolution of the actin crosslinking proteins journal May 1991
km23‐1/DYNLRB1 regulation of MEK/ERK signaling and R‐Ras in invasive human colorectal cancer cells journal August 2019
Self-made frits for nanoscale columns in proteomics journal October 2005
Membrance traffic wardens and protein secretion in Gram-negative bacteria journal January 1993
Prediction, Assessment and Validation of Protein Interaction Maps in Bacteria journal November 2002
[34] Ras-Raf interaction: Two-hybrid analysis book January 1995
Structural comparisons of calponin homology domains: implications for actin binding journal November 1998
Antibodies against gangliosides: a link between preceding infection and immunopathogenesis of GuillainBarré syndrome journal March 2002
Anti-Immunology: Evasion of the Host Immune System by Bacterial and Viral Pathogens journal February 2006
The effector repertoire of enteropathogenic E. coli: ganging up on the host cell journal February 2009
Cell-Penetrating Bacterial Effector Proteins: Better Tools than Targets journal February 2017
Chemically Etched Open Tubular and Monolithic Emitters for Nanoelectrospray Ionization Mass Spectrometry journal November 2006
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 journal August 1970
A complex of N-WASP and WIP integrates signalling cascades that lead to actin polymerization journal June 2000
The protein–protein interaction map of Helicobacter pylori journal January 2001
The fibronectin-binding motif within FlpA facilitates Campylobacter jejuni adherence to host cell and activation of host cell signaling journal January 2013
MS-GF+ makes progress towards a universal database search tool for proteomics journal October 2014
Toward a functional analysis of the yeast genome through exhaustive two-hybrid screens journal July 1997
Bacterial strategies for overcoming host innate and adaptive immune responses journal November 2002
Campylobacter jejuni: molecular biology and pathogenesis journal September 2007
Salmonella enterica serotype Typhimurium usurps the scaffold protein IQGAP1 to manipulate Rac1 and MAPK signalling journal November 2011
Identification and molecular cloning of a gene encoding a fibronectin‐binding protein (CadF) from Campylobacter jejuni journal June 1997
Bacterial secreted proteins are required for the internalization of Campylobacter jejuni into cultured mammalian cells journal May 1999
Salmonella type III secretion-associated chaperones confer secretion-pathway specificity: Type III secretion chaperones journal January 2004
Yersinia effectors target mammalian signalling pathways journal April 2002
Characterization of the Interactions between the Small GTPase Cdc42 and Its GTPase-activating Proteins and Putative Effectors journal August 1997
Injection of Flagellin into the Host Cell Cytosol by Salmonella enterica Serotype Typhimurium journal November 2007
Requirement for the Dynein Light Chain km23-1 in a Smad2-dependent Transforming Growth Factor-β Signaling Pathway journal June 2007
IQGAP1 Regulates Salmonella Invasion through Interactions with Actin, Rac1, and Cdc42 journal August 2007
Analysis of the Human Tissue-specific Expression by Genome-wide Integration of Transcriptomics and Antibody-based Proteomics journal December 2013
A porcine ligated loop model reveals new insight into the host immune response against Campylobacter jejuni journal September 2020
Manipulation of kinase signaling by bacterial pathogens journal November 2011
RCP-driven α5β1 recycling suppresses Rac and promotes RhoA activity via the RacGAP1–IQGAP1 complex journal September 2013
Secretion of the Virulence‐Associated Campylobacter Invasion Antigens from Campylobacter jejuni Requires a Stimulatory Signal journal June 2001
A Point-Source Outbreak of Campylobacteriosis Associated with Consumption of Raw Milk journal September 1985
Early Colonic Damage and Invasion of Campylobacter jejuni in Experimentally Challenged Infant Macaca mulatta journal July 1993
Kinetic and Antigenic Characterization of Altered Protein Synthesis by Campylobacter jejuni during Cultivation with Human Epithelial Cells journal October 1993
The InterPro database, an integrated documentation resource for protein families, domains and functional sites journal January 2001
CDD: NCBI's conserved domain database journal November 2014
The eukaryotic linear motif resource – 2018 update journal November 2017
The Pfam protein families database in 2019 journal October 2018
Type III secretion systems: the bacterial flagellum and the injectisome journal October 2015
Maximal adherence and invasion of INT 407 cells by Campylobacter jejuni requires the CadF outer-membrane protein and microfilament reorganization journal January 2003
Ca2+ release from host intracellular stores and related signal transduction during Campylobacter jejuni 81-176 internalization into human intestinal cells journal September 2005
Campylobacter jejuni activates mitogen-activated protein kinases in Caco-2 cell monolayers and in vitro infected primary human colonic tissue journal August 2005
Protein interaction mapping: A Drosophila case study journal February 2005
Role of Microfilaments and Microtubules in the Invasion of INT-407 Cells by Campylobacter jejuni journal June 2003
FlaC, a protein of Campylobacter jejuni TGH9011 (ATCC43431) secreted through the flagellar apparatus, binds epithelial cells and influences cell invasion: Secreted FlaC influences invasion journal June 2004
Identification of a fibronectin-binding domain within the Campylobacter jejuni CadF protein: C. jejuni fibronectin-binding protein journal July 2005
Identification and analysis of flagellar coexpressed determinants (Feds) of Campylobacter jejuni involved in colonization: Flagellar coexpressed determinants of C. jejuni journal March 2012
Role of the small Rho GTPases Rac1 and Cdc42 in host cell invasion of Campylobacter jejuni journal October 2007
Salmonella effectors: important players modulating host cell function during infection: Salmonella effectors journal October 2011
The cooperative action of bacterial fibronectin-binding proteins and secreted proteins promote maximal Campylobacter jejuni invasion of host cells by stimulating membrane ruffling: C. jejuni invasion of epithelial cells journal November 2011
Crystal structure of the repetitive segments of spectrin journal December 1993
Global Epidemiology of Campylobacter Infection journal June 2015
Identification of Campylobacter jejuni Genes Involved in Its Interaction with Epithelial Cells journal June 2010
Heterogeneity of a Campylobacter jejuni Protein That Is Secreted through the Flagellar Filament journal May 2007
Host-Pathogen Interactions: Basic Concepts of Microbial Commensalism, Colonization, Infection, and Disease journal December 2000
Secretion of Flagellar Proteins by the Pseudomonas aeruginosa Type III Secretion-Injectisome System journal April 2015
Campylobacter jejuni FlpA Binds Fibronectin and Is Required for Maximal Host Cell Adherence journal October 2009
YplA Is Exported by the Ysc, Ysa, and Flagellar Type III Secretion Systems of Yersinia enterocolitica journal March 2002
Secretion of Virulence Proteins from Campylobacter jejuni Is Dependent on a Functional Flagellar Export Apparatus journal May 2004
IQGAP1 Is a Scaffold for Mitogen-Activated Protein Kinase Signaling journal September 2005
Manipulation of Rab GTPase Function by Intracellular Bacterial Pathogens journal December 2007
Process of Protein Transport by the Type III Secretion System journal December 2004
Campylobacter colitis: histological immunohistochemical and ultrastructural findings. journal September 1985
A role for Campylobacter jejuni-induced enteritis in inflammatory bowel disease? journal January 2010
Transcriptome landscape of the human placenta journal January 2012
Invasion of epithelial cells by Campylobacter jejuni is independent of caveolae journal January 2013
The Campylobacter jejuni CiaD effector protein activates MAP kinase signaling pathways and is required for the development of disease journal January 2013
Serine phosphorylation of cortactin is required for maximal host cell invasion by Campylobacter jejuni journal January 2013
The signaling pathway of Campylobacter jejuni-induced Cdc42 activation: Role of fibronectin, integrin beta1, tyrosine kinases and guanine exchange factor Vav2 journal January 2011
The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists journal January 2007
Rac1 is deactivated at integrin activation sites through an IQGAP1–filamin-A–RacGAP1 pathway journal September 2013
The Salmonella SPI2 Effector SseI Mediates Long-Term Systemic Infection by Modulating Host Cell Migration journal November 2009
A Novel Mouse Model of Campylobacter jejuni Gastroenteritis Reveals Key Pro-inflammatory and Tissue Protective Roles for Toll-like Receptor Signaling during Infection journal July 2014
The Campylobacter jejuni CiaC virulence protein is secreted from the flagellum and delivered to the cytosol of host cells journal January 2012
Campylobacter jejuni Demonstrates Conserved Proteomic and Transcriptomic Responses When Co-cultured With Human INT 407 and Caco-2 Epithelial Cells journal April 2019
Cortactin: A multifunctional regulator of cellular invasiveness journal March 2011