ArticleCellular and molecular gastroenterology and hepatology2018
Attaching-and-Effacing Pathogens Exploit Junction Regulatory Activities of N-WASP and SNX9 to Disrupt the Intestinal Barrier.
Article in Cellular and molecular gastroenterology and hepatology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- RAB40C regulates SNX9 stabilityCentral-European journal of immunology · 2026Article
- EnterohemorrhagicPathogens (Basel, Switzerland) · 2025Article
- Effects of combined Bacillus coagulans and yeast fermentation culture on growth performance, plasma biochemical indices, intestinal morphology, and microbial of broilers.Journal of animal science · 2025Article
- Why put yourself on a pedestal? The pathogenic role of the A/E pedestal.Infection and immunity · 2024Review
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- EnterohemorrhagicInfection and immunity · 2024Article
- Changes of Ex Vivo Cervical Epithelial Cells Due to Electroporation with JMY.International journal of molecular sciences · 2023Article
- A Th17 cell-intrinsic glutathione/mitochondrial-IL-22 axis protects against intestinal inflammation.bioRxiv : the preprint server for biology · 2023Article
- Oral Administration with Live Attenuated Citrobacter rodentium Protects Immunocompromised Mice from Lethal Infection.Infection and immunity · 2022Article
- Actin cytoskeleton dynamics during mucosal inflammation: a view from broken epithelial barriers.Current opinion in physiology · 2021Article
- AnFrontiers in microbiology · 2021Article
- Article
- EnteropathogenicInternational journal of molecular sciences · 2020Article
- EnterohemorrhagicFrontiers in cell and developmental biology · 2020Article
- Bacteria That Cause Enteric Diseases Stimulate Distinct Humoral Immune Responses.Frontiers in immunology · 2020Review
- Coordinated transient interaction of ZO-1 and afadin is required for pedestal maturation induced by EspF from enteropathogenic Escherichia coli.MicrobiologyOpen · 2019Article
- EspF is crucial for Citrobacter rodentium-induced tight junction disruption and lethality in immunocompromised animals.PLoS pathogens · 2019Article
- Stinging Tight Junctions With WASPs.Cellular and molecular gastroenterology and hepatology · 2018Article
- Clever Cooperation: Interactions Between EspF and Host Proteins.Frontiers in microbiology · 2018Review
- Desmosome Disruption by EnteropathogenicCellular and molecular gastroenterology and hepatology · 2018Article
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsNeural Wiskott-Aldrich Syndrome protein (N-WASP) is a key regulator of the actin cytoskeleton in epithelial tissues and is poised to mediate cytoskeletal-dependent aspects of apical junction complex (AJC) homeostasis. Attaching-and-effacing (AE) pathogens disrupt this homeostasis through translocation of the effector molecule early secreted antigenic target-6 (ESX)-1 secretion-associated protein F (EspF). Although the mechanisms underlying AJC disruption by EspF are unknown, EspF contains putative binding sites for N-WASP and the endocytic regulator sorting nexin 9 (SNX9). We hypothesized that N-WASP regulates AJC integrity and AE pathogens use EspF to induce junction disassembly through an N-WASP- and SNX9-dependent pathway.
methodsWe analyzed mice with intestine-specific N-WASP deletion and generated cell lines with N-WASP and SNX9 depletion for dynamic functional assays. We generated EPEC and
resultsMice lacking N-WASP in the intestinal epithelium showed spontaneously increased permeability, abnormal AJC morphology, and mislocalization of occludin. N-WASP depletion in epithelial cell lines led to impaired assembly and disassembly of tight junctions in response to changes in extracellular calcium. Cells lacking N-WASP or SNX9 supported actin pedestals and type III secretion, but were resistant to EPEC-induced AJC disassembly and loss of transepithelial resistance. We found that during in vivo infection with AE pathogens, EspF must bind both N-WASP and SNX9 to disrupt AJCs and induce intestinal barrier dysfunction.
conclusionsOverall, these studies show that N-WASP critically regulates AJC homeostasis, and the AE pathogen effector EspF specifically exploits both N-WASP and SNX9 to disrupt intestinal barrier integrity during infection.
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