Evidence map›Paper›PMID 33109721›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

Phosphatidylinositol-4-kinase IIα licenses phagosomes for TLR4 signaling and MHC-II presentation in dendritic cells.

Cynthia López-Haber, Roni Levin-Konigsberg, Yueyao Zhu, Jing Bi-Karchin, Tamas Balla, Sergio Grinstein, Michael S Marks, Adriana R Mantegazza

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

12 citing papers in PubMed, 18 citations in OpenAlex.

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  10. Examining the Underappreciated Role ofFrontiers in immunology · 2021
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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

8 authors at 3 institutions in 2 countries.

Cynthia López-HaberDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104.ORCID 0000-0001-9106-543X
Roni Levin-KonigsbergDivision of Cell Biology, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
Yueyao ZhuDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
Jing Bi-KarchinDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104.
Tamas BallaSection on Molecular Signal Transduction, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892.
Sergio GrinsteinDivision of Cell Biology, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.ORCID 0000-0002-0795-4160
Michael S MarksDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104.ORCID 0000-0001-7435-7262
Adriana R MantegazzaDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104; adrim@pennmedicine.upenn.edu.ORCID 0000-0002-7583-0231
Children's Hospital of Philadelphia · USUniversity of Toronto · CAEunice Kennedy Shriver National Institute of Child Health and Human Development · US

Funding

Hermansky Pudlak Syndrome &melanosome formationR01EY015625 · NEI · UNIVERSITY OF PENNSYLVANIA · PI Michael S Marks · 2004 to 2026
$9.2M
Membrane trafficking in innate immunity to bacterial pathogensR01AI137173 · NIAID · THOMAS JEFFERSON UNIVERSITY · PI MANTEGAZZA, ADRIANA RITA · 2018 to 2022
$2.1M
Platelet granule formation and function in health and diseaseR01HL121323 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI MARKS, MICHAEL S · 2014 to 2017
$1.9M
NEI NIH HHS R01 EY015625NHLBI NIH HHS R01 HL121323NIAID NIH HHS R01 AI137173
6 · The paper itself

Abstract

Toll-like receptor (TLR) recruitment to phagosomes in dendritic cells (DCs) and downstream TLR signaling are essential to initiate antimicrobial immune responses. However, the mechanisms underlying TLR localization to phagosomes are poorly characterized. We show herein that phosphatidylinositol-4-kinase IIα (PI4KIIα) plays a key role in initiating phagosomal TLR4 responses in murine DCs by generating a phosphatidylinositol-4-phosphate (PtdIns4P) platform conducive to the binding of the TLR sorting adaptor Toll-IL1 receptor (TIR) domain-containing adaptor protein (TIRAP). PI4KIIα is recruited to maturing lipopolysaccharide (LPS)-containing phagosomes in an adaptor protein-3 (AP-3)-dependent manner, and both PI4KIIα and PtdIns4P are detected on phagosomal membrane tubules. Knockdown of PI4KIIα-but not the related PI4KIIβ-impairs TIRAP and TLR4 localization to phagosomes, reduces proinflammatory cytokine secretion, abolishes phagosomal tubule formation, and impairs major histocompatibility complex II (MHC-II) presentation. Phagosomal TLR responses in PI4KIIα-deficient DCs are restored by reexpression of wild-type PI4KIIα, but not of variants lacking kinase activity or AP-3 binding. Our data indicate that PI4KIIα is an essential regulator of phagosomal TLR signaling in DCs by ensuring optimal TIRAP recruitment to phagosomes.

Indexed as

1-Phosphatidylinositol 4-KinaseAnimalsBone Marrow CellsCytokinesDendritic CellsLipopolysaccharidesMajor Histocompatibility ComplexMicePhagosomesSignal TransductionToll-Like Receptor 4Toll-Like Receptors1-Phosphatidylinositol 4-KinaseCytokinesLipopolysaccharidesTlr4 protein, mouseToll-Like Receptor 4Toll-Like ReceptorsAP-3dendritic cellsMHC-IIPI4KIIαTIRAP

Identifiers

PMID33109721
PMCPMC7668187
OpenAlexW3097168712

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.