Related Experiment Video

Updated: Nov 17, 2025

Functional Characterization of RING-Type E3 Ubiquitin Ligases In Vitro and In Planta
10:27

Functional Characterization of RING-Type E3 Ubiquitin Ligases In Vitro and In Planta

Published on: December 5, 2019

9.2K

Apurinic/Apyrimidinic Endonuclease 1 Restricts the Internalization of Bacteria Into Human Intestinal Epithelial Cells

Gerco den Hartog1, Lindsay D Butcher1, Amber L Ablack1

  • 1Department of Medicine, Division of Gastroenterology, University of California San Diego, La Jolla, CA, United States.

Frontiers in Immunology
|February 19, 2021
PubMed

Insights

Apurinic/apyrimidinic endonuclease 1 (APE1) protein inhibits pathogenic intestinal bacteria entry into human cells by regulating Rac1. This process protects the intestinal epithelial barrier function from invasive bacteria.

Area of Science:

  • Microbiology
  • Cell Biology
  • Molecular Biology

Background:

  • Pathogenic intestinal bacteria cause significant human disease.
  • Understanding host-pathogen interactions in the intestinal epithelium is crucial for disease prevention.
  • The role of Apurinic/apyrimidinic endonuclease 1 (APE1) in bacterial internalization is not well understood.

Purpose of the Study:

  • To investigate the role of APE1 in regulating the internalization of pathogenic bacteria into intestinal epithelial cells.
  • To determine the effect of APE1 on Rho GTPase Rac1 activation and epithelial barrier function during bacterial infection.

Main Methods:

  • Infection of intestinal tumor cell lines and primary human epithelial cells with *Salmonella enterica* serovar Typhimurium and *Escherichia coli*.
  • Assessment of bacterial internalization, Rac1 regulation, and epithelial cell barrier function following APE1 inhibition.
  • Pharmacological inhibition and overexpression of Rac1 were used to elucidate its role in bacterial internalization.

Main Results:

  • APE1-deficient cells showed increased internalization of *Salmonella* and *E. coli*.
  • Bacterial infection activated Rac1, but APE1 negatively regulated this activation.
  • Inhibition of Rac1 reduced intracellular bacteria in APE1-deficient cells, while Rac1 overexpression increased bacterial numbers in APE1-competent cells.
  • Increased intracellular bacteria led to loss and delayed recovery of epithelial barrier function.

Conclusions:

  • APE1 inhibits the internalization of invasive bacteria into human intestinal epithelial cells.
  • APE1 exerts its inhibitory effect by negatively regulating Rac1.
  • APE1 plays a protective role in maintaining intestinal epithelial barrier function against invasive bacteria.
Keywords:
AIEC LF82 strainRac1Salmonella Typhimuriumapurinic/apyrimidinic endonuclease 1internalizationintestinal epithelial barrierinvasion

More Related Videos

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

11.1K
Assessment of Intestinal Transcytosis of Neonatal Escherichia coli Bacteremia Isolates08:32

Assessment of Intestinal Transcytosis of Neonatal Escherichia coli Bacteremia Isolates

Published on: February 17, 2023

1.6K

Related Concept Videos

Restriction Enzymes01:11

Restriction Enzymes

Restriction enzymes are bacterial enzymes used to cut DNA in a sequence-specific manner. To cleave DNA, they bind to specific palindromic sequences called restriction sites. Such palindromic DNA sequences or inverted repeats are commonly found in regions of functional significance, such as the origin of replication, gene operator sites, and regions containing transcription termination signals.
The host bacteria protect their own genomic DNA from these enzymes by methylating these sites. Some...
33.9K
Directionality of Nuclear Transport01:42

Directionality of Nuclear Transport

Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of  Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...
4.0K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
6.4K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.8K
Recycling Endosomes and Transcytosis00:58

Recycling Endosomes and Transcytosis

The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
3.2K
Types of RNA01:23

Types of RNA

Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
70.8K