Evidence map›Paper›PMID 35143768›Full record

ArticleCell host & microbe2022

Depletion of the apical endosome in response to viruses and bacterial toxins provides cell-autonomous host defense at mucosal surfaces.

Keiko Maeda, Nicholas C Zachos, Megan H Orzalli, Stefanie S Schmieder, Denis Chang, Katlynn Bugda Gwilt, Michele Doucet, Nicholas W Baetz, Sun Lee, Sue E Crawford and 4 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell host & microbe, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.1field-weighted citation impact, top 29% 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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. 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

14 authors at 5 institutions in 1 country.

Keiko MaedaDivision of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Nicholas C ZachosDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Megan H OrzalliDivision of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Stefanie S SchmiederDivision of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Denis ChangDivision of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Katlynn Bugda GwiltDivision of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Michele DoucetDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Nicholas W BaetzDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Sun LeeDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Sue E CrawfordDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, MS: BCM-385, Houston, TX 77030, USA.
Mary K EstesDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, MS: BCM-385, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Jonathan C KaganDivision of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA; Harvard Digestive Diseases Center, Harvard Medical School, Boston, MA 02115, USA.
Jerrold R TurnerHarvard Digestive Diseases Center, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Wayne I LencerDivision of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA; Harvard Digestive Diseases Center, Harvard Medical School, Boston, MA 02115, USA. Electronic address: wayne.lencer@childrens.harvard.edu.
Boston Children's Hospital · USHarvard University · USJohns Hopkins University · USBaylor College of Medicine · USJohns Hopkins Medicine · US

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
Tissue Analysis & Molecular Imaging CoreP30DK056338 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI James Versalovic · 2001 to 2026
$28.3M
ZO-1-MEDIATED PROTEIN INTERACTIONS: REGULATORS AND INTEGRATORS OF DIVERSE EPITHELIAL FUNCTIONS IN HEALTH AND DISEASER01DK061931 · NIDDK · UNIVERSITY OF CHICAGO · PI JERROLD R. TURNER · 2001 to 2026
$15.0M
COngenital Diarrhea and Enteropathy (PediCODE) Consortium and BioRepositoryRC2DK118640 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI James Richard Goldenring, Izumi Kaji · 2019 to 2026
$14.8M
Novel Platforms for Human Intestinal Enteroids: Matrix, Mechanics, and TopographyU19AI116497 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI GRANDE-ALLEN, KATHRYN JANE · 2015 to 2025
$13.2M
Translational Research Enhancement CoreP30DK089502 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI ZACHOS, NICHOLAS CONSTANTINE · 2011 to 2020
$12.0M
Therapeutic targeting of protein interactions to reverse MLCK1-mediated intestinal barrier loss and ameliorate disease.R01DK068271 · NIDDK · UNIVERSITY OF CHICAGO · PI JERROLD R. TURNER · 2005 to 2026
$11.3M
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
Translational Approaches to Develop Drug Therapy for DiarrheaR24DK099803 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DONOWITZ, MARK · 2014 to 2019
$8.9M
Regulation of Rotavirus ReplicationR01AI080656 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI Sue Ellen Crawford, Mary Kolb Estes · 2009 to 2026
$7.9M
Intestinal Disease-enterocyte toxin interactionR37DK048106 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI LENCER, WAYNE I · 2011 to 2020
$7.0M
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
NIAID NIH HHS R01 AI080656NIAID NIH HHS U19 AI116497NIDDK NIH HHS P30 DK034854NIDDK NIH HHS P30 DK056338NIDDK NIH HHS P30 DK089502NIDDK NIH HHS R01 DK048106NIDDK NIH HHS R01 DK061931NIDDK NIH HHS R01 DK068271NIDDK NIH HHS R01 DK084424NIDDK NIH HHS R01 DK104868NIDDK NIH HHS R24 DK099803NIDDK NIH HHS R37 DK048106NIDDK NIH HHS RC2 DK118640
6 · The paper itself

Abstract

Polarized epithelial cells form an essential barrier against infection at mucosal surfaces. Many pathogens breach this barrier to cause disease, often by co-opting cellular endocytosis mechanisms to enter the cell through the lumenal (apical) cell surface. We recently discovered that the loss of the cell polarity gene PARD6B selectively diminishes apical endosome function. Here, we find that in response to the entry of certain viruses and bacterial toxins into the epithelial cells via the apical membrane, PARD6B and aPKC, two components of the PARD6B-aPKC-Cdc42 apical polarity complex, undergo rapid proteasome-dependent degradation. The perturbation of apical membrane glycosphingolipids by toxin- or virus-binding initiates degradation of PARD6B. The loss of PARD6B causes the depletion of apical endosome function and renders the cell resistant to further infection from the lumenal cell surface, thus enabling a form of cell-autonomous host defense.

Indexed as

Bacterial ToxinsVirusesCell PolarityEndosomesEpithelial CellsProtein Kinase CBacterial ToxinsProtein Kinase Capical endosomeaPKCCdc42enteroidsglycosphingolipidshost defensePARD6Brotavirustrafficking

Identifiers

PMID35143768
PMCPMC8852832
OpenAlexW4210855390

What OpenQuestion holds

Textmetadata
LicenceTDM
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.