Evidence map›Paper›PMID 21041954›Full record

ArticleThe Journal of clinical investigation2010

Intoxication of zebrafish and mammalian cells by cholera toxin depends on the flotillin/reggie proteins but not Derlin-1 or -2.

David E Saslowsky, Jin Ah Cho, Himani Chinnapen, Ramiro H Massol, Daniel J-F Chinnapen, Jessica S Wagner, Heidi E De Luca, Wendy Kam, Barry H Paw, Wayne I Lencer

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
3.7field-weighted citation impact, top 7% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 83 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Zebrafish embryo sensitivity test as in vivo platform to anti-Shiga toxin compound screening.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2020
    Article
  9. Flotillins: At the Intersection of ProteinInternational journal of molecular sciences · 2020
    Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

David E SaslowskyDivision of Gastroenterology, Children's Hospital, Boston, Massachusetts, USA.
Jin Ah Cho
Himani Chinnapen
Ramiro H Massol
Daniel J-F Chinnapen
Jessica S Wagner
Heidi E De Luca
Wendy Kam
Barry H Paw
Wayne I Lencer
Boston Children's Hospital · USBrigham and Women's Hospital · US

Funding

TRANSCRIPTION FACTOR GATA-1 IN TERMINAL ERYTHROID DEVELOPMENTP01HL032262 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI BAUER, DANIEL EVAN · 1985 to 2021
$38.9M
STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
Mechanism of action for the epithelial-specific ER stress sensor IRE1β in regulating intestinal homeostasis and host defenseR01DK048106 · NIDDK · CHILDREN'S HOSPITAL BOSTON · PI WAYNE I LENCER · 1993 to 2026
$9.6M
Crystallography CoreP30DK072437 · NIDDK · UNIVERSITY OF UTAH · PI KAPLAN, JERRY · 2005 to 2010
$4.0M
FcRn-dependent sorting of IgG and IgG-opsinized antigens by epithelial cellsR01DK084424 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI LENCER, WAYNE I · 2009 to 2013
$1.9M
Frascati: mitochondrial transporter and erythropoiesisR01DK070838 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI PAW, BARRY H · 2007 to 2011
$1.8M
Glycolipid Trafficking of Cholera Toxin by Lipid RaftsK01DK073480 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI SASLOWSKY, DAVID E · 2006 to 2010
$646k
Retrotranslocation of cholera toxin AI-chain from ER ot cytosol and cell responseF32DK083894 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI CHO, JIN AH · 2009 to 2010
$98k
NHLBI NIH HHS P01 HL032262NIDDK NIH HHS DK0484424NIDDK NIH HHS F32 DK083894NIDDK NIH HHS K01 DK073480NIDDK NIH HHS P30 DK034854NIDDK NIH HHS P30 DK072437NIDDK NIH HHS P30 DK34854NIDDK NIH HHS R01 DK048106NIDDK NIH HHS R01 DK070838NIDDK NIH HHS R01 DK084424NIDDK NIH HHS R01 DK48106
6 · The paper itself

Abstract

Cholera toxin (CT) causes the massive secretory diarrhea associated with epidemic cholera. To induce disease, CT enters the cytosol of host cells by co-opting a lipid-based sorting pathway from the plasma membrane, through the trans-Golgi network (TGN), and into the endoplasmic reticulum (ER). In the ER, a portion of the toxin is unfolded and retro- translocated to the cytosol. Here, we established zebrafish as a genetic model of intoxication and examined the Derlin and flotillin proteins, which are thought to be usurped by CT for retro-translocation and lipid sorting, respectively. Using antisense morpholino oligomers and siRNA, we found that depletion of Derlin-1, a component of the Hrd-1 retro-translocation complex, was dispensable for CT-induced toxicity. In contrast, the lipid raft-associated proteins flotillin-1 and -2 were required. We found that in mammalian cells, CT intoxication was dependent on the flotillins for trafficking between plasma membrane/endosomes and two pathways into the ER, only one of which appears to intersect the TGN. These results revise current models for CT intoxication and implicate protein scaffolding of lipid rafts in the endo-somal sorting of the toxin-GM1 complex.

Indexed as

AnimalsBase SequenceBiological Transport, ActiveCell LineChlorocebus aethiopsCholera ToxinCOS CellsEndosomesG(M1) GangliosideHumansMembrane MicrodomainsMembrane ProteinsRNA, Small InterferingZebrafishZebrafish ProteinsCholera ToxinDERL1 protein, humanDERL2 protein, humanflotillinsG(M1) GangliosideMembrane ProteinsRNA, Small InterferingZebrafish Proteins

Identifiers

PMID21041954
PMCPMC2994338
OpenAlexW2078759384

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.