IQGAP1 in microbial pathogenesis: Targeting the actin cytoskeleton

Kim, Hugh; White, Colin D.; Sacks, David B.

doi:10.1016/j.febslet.2011.01.041

Cited by 39 publications

(39 citation statements)

References 87 publications

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“…IQGAP1 has been implicated as a target of several bacteria as a player in their mechanisms of infection. Salmonella typhimurium has been shown to bind to IQGAP1 which allows S. typhimurium to escape the host immune response allowing for the establishment of chronic infection (Kim et al 2011). Additionally, IQGAP1 was found to be needed to organize ROS-dependent VEGF signaling via VEGFR2 in endothelial cells which may contribute to the repair and maintenance of blood vessels and angiogenesis (Yamaoka-Tojo et al 2004).…”

Section: Discussionmentioning

confidence: 99%

A Genome-Wide Association Study of Chronic Otitis Media with Effusion and Recurrent Otitis Media Identifies a Novel Susceptibility Locus on Chromosome 2

Allen

Chen

Weeks

et al. 2013

JARO

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Chronic otitis media with effusion (COME) and recurrent otitis media (ROM) have been shown to be heritable, but candidate gene and linkage studies to date have been equivocal. Our aim was to identify genetic susceptibility factors using a genome-wide association study (GWAS). We genotyped 602 subjects from 143 families with 373 COME/ROM subjects using the Illumina Human CNV370-Duo DNA Bead Chip (324,748 SNPs). We carried out the GWAS scan and imputed SNPs at the regions with the most significant associations. Replication genotyping in an independent family-based sample was conducted for 53 SNPs: the 41 most significant SNPs with PG10 −4 and 12 imputed SNPs with PG10 −4 on chromosome 15 (near the strongest signal). We replicated the association of rs10497394 (GWAS discovery P= 1.30×10 −5 ) on chromosome 2 in the independent otitis media population (P=4.7×10 −5 ; meta-analysis P= 1.52×10 −8 ). Three additional SNPs had replication PvaluesG0.10. Two were on chromosome 15q26.1 including rs1110060, the strongest association with COME/ROM in the primary GWAS (P=3.4×10 −7 ) in KIF7 intron 7 (P=0.072), and rs10775247, a nonsynonymous SNP in TICRR exon 2 (P=0.075). The third SNP rs386057 was on chromosome 5 in TPPP intron 1 (P=0.045). We have performed the first GWAS of COME/ROM and have identified a SNP rs10497394 on chromosome 2 is significantly associated with COME/ROM susceptibility. This SNP is within a 537 kb intergenic region, bordered by CDCA7 and SP3. The genomic and functional significance of this newly identified locus in COME/ROM pathogenesis requires additional investigation.

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Section: Discussionmentioning

confidence: 99%

A Genome-Wide Association Study of Chronic Otitis Media with Effusion and Recurrent Otitis Media Identifies a Novel Susceptibility Locus on Chromosome 2

Allen

Chen

Weeks

et al. 2013

JARO

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“…Moreover, it has been shown that Tir of EPEC can also bind to the host cell multidomain protein IQGAP1, a well-known regulator of the cy- toskeleton, involved in Rho family GTPases Rac1/Cdc42 and Ca 2+ /calmodulin signaling, and actin polymerization. [19][20][21] On the other hand, Brown et al also demonstrated that although cells lacking protein IQGAP1 have significantly attenuated actin polymerization in response to EPEC attachment, the knockout of IQGAP1 did not abrogate pedestal formation. 20 Peralta-Ramirez et al in their study of REPEC strain demonstrated that EspF protein secreted by A/E pathogens via TTSS to a host cell is involved in the regulation of actin polymerization by binding to a complex of proteins, e.g., N-WASP and Arp2/3, but also to ZO-1, ZO-2 proteins at the TJs.…”

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confidence: 99%

Intestinal epithelial barrier: The target for pathogenic Escherichia coli

Pawłowska¹,

Sobieszczańska²

2017

Adv Clin Exp Med

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Diarrheagenic Escherichia coli strains are included in 9 pathotypes (pathovars) that present different virulence factors responsible for the patomechanism of infections they cause. As all other intestinal pathogens, E. coli exerts a significant effect on intestinal epithelium. To initiate the infection, these microorganisms have evolved countless strategies to subvert the epithelial barrier and efficiently colonize the intestinal epithelium. The barrier function of the intestinal epithelium is achieved by the presence of a tight junction protein network surrounding individual cells around their circumference that links neighboring cells and seals the intracellular space. Pathogenic E. coli strains may impair intestinal epithelial barrier in 3 different pathways: (i) through a direct effect of their virulence factors on tight junctions proteins, (ii) by disrupting host cell actin cytoskeleton that indirectly damages epithelial barrier, and (iii) via stimulation of the secretion of proinflammatory cytokines that directly disrupt epithelial tight junctions or trigger neutrophils migration through intestinal epithelium, thus disrupting the intestinal barrier. Most pathogenic E. coli generates all these 3 pathways concomitantly upon interaction with intestinal epithelium.

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“…For example, filopodia significantly increase the ability of filoviruses to spread from cell to cell, thereby contributing to pathogenesis (10). One multifunctional host protein that plays key roles in regulating cell motility, cytoskeletal architecture, actin polymerization, and formation of filopodia is IQGAP1 (11)(12)(13)(14)(15)(16). Indeed, IQGAP1 is a widely expressed scaffolding protein with multiple proteinprotein interaction domains, including a WW-domain that may interact with viral PPxY type L-domains (12).…”

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confidence: 99%

Host IQGAP1 and Ebola Virus VP40 Interactions Facilitate Virus-Like Particle Egress

Liu

et al. 2013

J Virol

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We have identified host IQGAP1 as an interacting partner for Ebola virus (EBOV) VP40, and its expression is required for EBOV VP40 virus-like particle (VLP) budding. IQGAP1 is involved in actin cytoskeletal remodeling during cell migration and formation of filopodia. The physical interaction and the functional requirement for IQGAP1 in EBOV VP40 VLP egress link virus budding to the cytoskeletal remodeling machinery. Consequently, this interaction represents a novel target for development of therapeutics to block budding and transmission of filoviruses. E bola virus (EBOV) and Marburg virus (MARV) are enveloped, negative-sense RNA viruses belonging to the family Filoviridae which cause hemorrhagic syndromes with high mortality rates in humans (1, 2). There are currently no licensed vaccines or therapeutics to control filovirus infection and transmission. The filovirus VP40 matrix protein plays a central role in virion assembly and egress such that independent expression of VP40 leads to the production of virus-like particles (VLPs) that accurately mimic budding of live virus (3-7). Late (L) budding domains of VP40, which recruit host proteins (e.g., Tsg101) required for efficient virus-cell separation (or "pinching-off"), consist of core consensus amino acid motifs such as PPxY, P(T/S)AP, YxxL, or FPIV (x ϭ any amino acid). The conservation of L-domains within matrix proteins of many RNA viruses suggests that they are generally important and required for efficient RNA virus budding (8), although they are not absolutely required for viral replication (9).Unlike the events that contribute to the late stages of filovirus budding, little is known about the regulation of early stages of filovirus budding, but this likely involves cellular mechanisms that control cytoskeletal remodeling and membrane deformation/curvature. For example, filopodia significantly increase the ability of filoviruses to spread from cell to cell, thereby contributing to pathogenesis (10). One multifunctional host protein that plays key roles in regulating cell motility, cytoskeletal architecture, actin polymerization, and formation of filopodia is IQGAP1 (11-16). Indeed, IQGAP1 is a widely expressed scaffolding protein with multiple proteinprotein interaction domains, including a WW-domain that may interact with viral PPxY type L-domains (12). Intriguingly, IQGAP1 has been detected in purified HIV-1 virions (17) and has been shown to interact with the Gag protein of Moloney murine leukemia virus (MuLV) (18) and the core protein of classical swine fever virus (CSFV) (19) as well as host Tsg101 (20).Here we investigated whether endogenous IQGAP1 interacts with EBOV VP40 and whether this interaction regulates efficient egress of EBOV VP40 VLPs. We found that EBOV VP40 interacts with endogenous IQGAP1 and that the L-domain region of VP40 mediates this interaction. Importantly, we found that egress of EBOV VP40 VLPs from IQGAP1-suppressed cells is reduced. Together, our findings identify a functional requirement for IQGAP1 interactions with EBOV VP...

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IQGAP1 in microbial pathogenesis: Targeting the actin cytoskeleton

Cited by 39 publications

References 87 publications

A Genome-Wide Association Study of Chronic Otitis Media with Effusion and Recurrent Otitis Media Identifies a Novel Susceptibility Locus on Chromosome 2

A Genome-Wide Association Study of Chronic Otitis Media with Effusion and Recurrent Otitis Media Identifies a Novel Susceptibility Locus on Chromosome 2

Intestinal epithelial barrier: The target for pathogenic Escherichia coli

Host IQGAP1 and Ebola Virus VP40 Interactions Facilitate Virus-Like Particle Egress

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