ArticleMolecular biology of the cell2013
Shiga toxin-binding site for host cell receptor GPP130 reveals unexpected divergence in toxin-trafficking mechanisms.
Article in Molecular biology of the cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- Shedding of GPP130 by PC7 and Furin: Potential Implication in Lung Cancer Progression.International journal of molecular sciences · 2025Article
- Structural basis for neutralizing antibody binding to pertussis toxin.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- The Cellular and Chemical Biology of Endocytic Trafficking and Intracellular Delivery-The GL-Lect Hypothesis.Molecules (Basel, Switzerland) · 2021Review
- Review
- Blood group P1 antigen-bearing glycoproteins are functional but less efficient receptors of Shiga toxin than conventional glycolipid-based receptors.The Journal of biological chemistry · 2020Article
- Targeting the Early Endosome-to-Golgi Transport of Shiga Toxins as a Therapeutic Strategy.Toxins · 2020Review
- Functional dissection of the retrograde Shiga toxin trafficking inhibitor Retro-2.Nature chemical biology · 2020Article
- Article
- ZIP14 is degraded in response to manganese exposure.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2019Article
- Tamoxifen blocks retrograde trafficking of Shiga toxin 1 and 2 and protects against lethal toxicosis.Life science alliance · 2019Article
- Functional analyses of the UDP-galactose transporter SLC35A2 using the binding of bacterial Shiga toxins as a novel activity assay.Glycobiology · 2019Article
- Humanised monoclonal antibodies neutralise pertussis toxin by receptor blockade and reduced retrograde trafficking.Cellular microbiology · 2018Article
- Golgi integral membrane protein 4 manipulates cellular proliferation, apoptosis, and cell cycle in human head and neck cancer.Bioscience reports · 2018Article
- Protein Toxins That Utilize Gangliosides as Host Receptors.Progress in molecular biology and translational science · 2018Review
- Hypothyroidism induced by loss of the manganese efflux transporter SLC30A10 may be explained by reduced thyroxine production.The Journal of biological chemistry · 2017Article
- Genome-wide siRNA screen identifies UNC50 as a regulator of Shiga toxin 2 trafficking.The Journal of cell biology · 2017Article
- Shiga Toxin Therapeutics: Beyond Neutralization.Toxins · 2017Review
- Manganese-induced trafficking and turnover of GPP130 is mediated by sortilin.Molecular biology of the cell · 2017Article
- Protection against Shiga Toxins.Toxins · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Shiga toxicosis is caused by retrograde trafficking of one of three types of Shiga toxin (STx), STx, STx1, or STx2. Trafficking depends on the toxin B subunits, which for STx and STx1 are identical and bind GPP130, a manganese (Mn)-sensitive intracellular trafficking receptor. Elevated Mn down-regulates GPP130, rendering STx/STx1 harmless. Its effectiveness against STx2, however, which is a serious concern in the developed world, is not known. Here we show that Mn-induced GPP130 down-regulation fails to block STx2 trafficking. To shed light on this result, we tested the purified B subunit of STx2 for binding to GPP130 and found that it failed to interact. We then mapped residues at the interface of the GPP130-STx/STx1 complex. In GPP130, binding mapped to a seven-residue stretch in its lumenal stem domain next to the transmembrane domain. This stretch was required for STx/STx1 transport. In STx/STx1, binding mapped to a histidine-asparagine pair on a surface-exposed loop of the toxin B subunit. Significantly, these residues are not conserved in STx2, explaining the lack of effectiveness of Mn against STx2. Together our results imply that STx2 uses an evolutionarily distinct trafficking mechanism and that Mn as a potential therapy should be focused on STx/STx1 outbreaks, which account for the vast majority of cases worldwide.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.