Evidence map›Paper›PMID 33232321›Full record

ArticlePloS one2020

Aquaporin-3 regulates endosome-to-cytosol transfer via lipid peroxidation for cross presentation.

Sam C Nalle, Rosa Barreira da Silva, Hua Zhang, Markus Decker, Cecile Chalouni, Min Xu, George Posthuma, Ann de Mazière, Judith Klumperman, Adriana Baz Morelli and 5 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

21 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
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  7. Article
  8. Review
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  10. Article
  11. Channeling antigens to CD8Science (New York, N.Y.) · 2023
    Article
  12. The evolving biology of cross-presentation.Seminars in immunology · 2023
    Review
  13. Review
  14. Review
  15. Article
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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

15 authors at 5 institutions in 3 countries.

Sam C NalleDepartment of Cancer Immunology, Genentech, South San Francisco, California, United States of America.ORCID 0000-0002-8562-0860
Rosa Barreira da SilvaDepartment of Cancer Immunology, Genentech, South San Francisco, California, United States of America.
Hua ZhangDepartment of Immunology, Genentech Inc., South San Francisco, California, United States of America.
Markus DeckerDepartment of Cancer Immunology, Genentech, South San Francisco, California, United States of America.
Cecile ChalouniDepartment of Cancer Immunology, Genentech, South San Francisco, California, United States of America.
Min XuDepartment of Immunology, Genentech Inc., South San Francisco, California, United States of America.
George PosthumaDepartment of Cell Biology, University Medical Center Utrecht, Utrecht, The Netherlands.
Ann de MazièreDepartment of Cell Biology, University Medical Center Utrecht, Utrecht, The Netherlands.
Judith KlumpermanDepartment of Cell Biology, University Medical Center Utrecht, Utrecht, The Netherlands.
Adriana Baz MorelliCSL Ltd., Parkville, Victoria, Australia.
Sebastian J FleireNew York University Cancer Institute, New York, New York, United States of America.
Alan S VerkmanDepartment of Medicine, University of California, San Francisco, California, United States of America.
E Sergio TrombettaBoehringer Ingelheim, Ridgefield, Connecticut, United States of America.
Matthew L AlbertDepartment of Cancer Immunology, Genentech, South San Francisco, California, United States of America.ORCID 0000-0001-7285-6973
Ira MellmanDepartment of Cancer Immunology, Genentech, South San Francisco, California, United States of America.
University Medical Center Utrecht · NLBoehringer Ingelheim (United States) · USCSL (Australia) · AUNew York University · USUniversity of California, San Francisco · US

Funding

SynthesisP30DK072517 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2005 to 2022
$18.1M
Functional Role of Aquaporins in Eye PhysiologyR01EY013574 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2002 to 2022
$7.6M
MECHANISMS OF WATER TRANSPORT IN RENAL EPITHELIAR37DK035124 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 1999 to 2008
$4.2M
NEI NIH HHS R01 EY013574NIDDK NIH HHS P30 DK072517NIDDK NIH HHS R37 DK035124
6 · The paper itself

Abstract

Antigen cross presentation, whereby exogenous antigens are presented by MHC class I molecules to CD8+ T cells, is essential for generating adaptive immunity to pathogens and tumor cells. Following endocytosis, it is widely understood that protein antigens must be transferred from endosomes to the cytosol where they are subject to ubiquitination and proteasome degradation prior to being translocated into the endoplasmic reticulum (ER), or possibly endosomes, via the TAP1/TAP2 complex. Revealing how antigens egress from endocytic organelles (endosome-to-cytosol transfer, ECT), however, has proved vexing. Here, we used two independent screens to identify the hydrogen peroxide-transporting channel aquaporin-3 (AQP3) as a regulator of ECT. AQP3 overexpression increased ECT, whereas AQP3 knockout or knockdown decreased ECT. Mechanistically, AQP3 appears to be important for hydrogen peroxide entry into the endosomal lumen where it affects lipid peroxidation and subsequent antigen release. AQP3-mediated regulation of ECT was functionally significant, as AQP3 modulation had a direct impact on the efficiency of antigen cross presentation in vitro. Finally, AQP3-/- mice exhibited a reduced ability to mount an anti-viral response and cross present exogenous extended peptide. Together, these results indicate that the AQP3-mediated transport of hydrogen peroxide can regulate endosomal lipid peroxidation and suggest that compromised membrane integrity and coordinated release of endosomal cargo is a likely mechanism for ECT.

Indexed as

AnimalsAntigen PresentationAquaporin 3Biological TransportCells, CulturedCytosolEndosomesGene Knockout TechniquesHEK293 CellsHumansLipid PeroxidationMiceAQP3 protein, humanAqp3 protein, mouseAquaporin 3

Identifiers

PMID33232321
PMCPMC7685505
OpenAlexW3108585924

What OpenQuestion holds

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LicenceCC BY
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.