37-kDa Laminin Receptor Precursor Modulates Cytotoxic Necrotizing Factor 1–mediated RhoA Activation and Bacterial Uptake
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Cytotoxic necrotizing factor 1 (CNF1) is a bacterial toxin known to activate Rho GTPases and induce host cell cytoskeleton rearrangements. The constitutive activation of Rho GTPases by CNF1 is shown to enhance bacterial uptake in epithelial cells and human brain microvascular endothelial cells. However, it is unknown how exogenous CNF1 exhibits such phenotypes in eukaryotic cells. Here, we identified 37-kDa laminin receptor precursor (LRP) as the receptor for CNF1 from screening the cDNA library of human brain microvascular endothelial cells by the yeast two-hybrid system using the N-terminal domain of CNF1 as bait. CNF1-mediated RhoA activation and bacterial uptake were inhibited by exogenous LRP or LRP antisense oligodeoxynucleotides, whereas they were increased in LRP-overexpressing cells. These findings indicate that the CNF1 interaction with LRP is the initial step required for CNF1-mediated RhoA activation and bacterial uptake in eukaryotic cells.
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Other meningeal pathogens bind ECM components and receptors to mediate bacterial-BBB interactions.
“Other meningeal pathogens, such as Streptococcus pneumoniae (SPN), E. coli K1, Neisseria meningitidis, and Haemophilus influenza type B (HiB, also bind ECM components and ECM receptors (e.g., integrins and laminin receptor) to mediate bacterial-BBB interactions (12)(13)(14)(15).”
From Bacterial induction of Snail1 contributes to blood-brain barrier disruption (2015) · cites this paper as [13]
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Meningitis-Associated Escherichia coli
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Self-citation
- Authors
- Chung, J. W., Hong, S. J., Kim, K. J., Goti, D., Stins, M. F., Shin, S., Dawson, V. L., Dawson, T. M., & Kim, K. S.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Kim, Kwang Sik
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-05
- Volume
- 278
- Issue
- 19
- Pages
- 16857-16862
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2039475868
- Cited by
- 127
- References
- 38
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 16 · 2020: 2 · 2019: 2 · 2018: 6 · 2017: 2 · 2016: 4 · 2015: 8 · 2014: 8 · 2013: 5 · 2012: 6
- FWCI
- 3.34
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
- Life Sciences › Immunology and Microbiology › Immunology › Toxin Mechanisms and Immunotoxins
- Keywords
- cytotoxic necrotizing factor 1, RhoA activation, bacterial internalization, Rho GTPases, toxin receptor, brain microvascular endothelial cells, cytoskeleton rearrangement, host-pathogen interaction, antisense oligodeoxynucleotides
- MeSH terms
- Bacterial Toxins, Cell Line, Cytotoxins, Endothelium, Vascular, Enzyme Activation, Escherichia coli, Escherichia coli Infections, Protein Binding, Protein Precursors, Signal Transduction, Oligonucleotides, Antisense, Receptors, Laminin, rhoA GTP-Binding Protein, Escherichia coli Proteins
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