Evidence map›Paper›PMID 37225719›Full record

ArticleNature communications2023

A ZFYVE21-Rubicon-RNF34 signaling complex promotes endosome-associated inflammasome activity in endothelial cells.

Xue Li, Quan Jiang, Guiyu Song, Mahsa Nouri Barkestani, Qianxun Wang, Shaoxun Wang, Matthew Fan, Caodi Fang, Bo Jiang, Justin Johnson and 4 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

9 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Roles of endothelial cells during infection.Current opinion in immunology · 2025
    Review
  8. Article
  9. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 1 institution in 2 countries.

Xue Li *VA Connecticut Healthcare System, West Haven, CT, USA.
Quan Jiang *VA Connecticut Healthcare System, West Haven, CT, USA.ORCID http://orcid.org/0000-0001-8201-6417
Guiyu Song *VA Connecticut Healthcare System, West Haven, CT, USA. guiyu.song@yale.edu.
Mahsa Nouri BarkestaniVA Connecticut Healthcare System, West Haven, CT, USA.
Qianxun WangVA Connecticut Healthcare System, West Haven, CT, USA.ORCID http://orcid.org/0000-0001-9196-7505
Shaoxun WangVA Connecticut Healthcare System, West Haven, CT, USA.
Matthew FanYale College, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-4042-6685
Caodi FangVA Connecticut Healthcare System, West Haven, CT, USA.
Bo JiangDepartment of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT, USA.
Justin JohnsonDept of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Arnar GeirssonDept of Surgery, Yale University School of Medicine, New Haven, CT, USA.
George TellidesDept of Surgery, Yale University School of Medicine, New Haven, CT, USA.
Jordan S PoberDept of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-5990-1071
Dan Jane-WitVA Connecticut Healthcare System, West Haven, CT, USA. dan.jane-wit@yale.edu.ORCID http://orcid.org/0000-0001-7115-0362
Yale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Liver CenterP30DK034989 · NIDDK · YALE UNIVERSITY · PI WAJAHAT Zafar MEHAL · 1986 to 2026
$31.1M
THE ROLE OF ZFYVE21 IN CEREBRAL AMYLOID ANGIOPATHY IN ALZHEIMER'S DISEASER01HL141137 · NHLBI · YALE UNIVERSITY · PI JANE-WIT, DANIEL · 2018 to 2022
$2.6M
Ex Vivo Nanoparticle Drug Delivery Targeted to Human Renal Allograft EndotheliumU01AI132895 · NIAID · YALE UNIVERSITY · PI POBER, JORDAN S, SALTZMAN, W. MARK · 2017 to 2021
$2.2M
Intracellular Membrane Attack Complexes and COVID-19 Immune HyperactivationR21AI178582 · NIAID · YALE UNIVERSITY · PI JANE-WIT, DANIEL · 2023 to 2024
$461k
Hedgehog-Induced Activation of Alloimmune T Cells During Ischemia Reperfusion InjuryI01BX005117 · VA · VA CONNECTICUT HEALTHCARE SYSTEM · PI JANE-WIT, DANIEL · 2021 to 2024
–
BLRD VA I01 BX005117NCATS NIH HHS UL1 TR001863NHLBI NIH HHS R01 HL141137NIAID NIH HHS R21 AI178582NIAID NIH HHS U01 AI132895NIDDK NIH HHS P30 DK034989
6 · The paper itself

Abstract

Internalization of complement membrane attack complexes (MACs) assembles NLRP3 inflammasomes in endothelial cells (EC) and promotes IL-β-mediated tissue inflammation. Informed by proteomics analyses of FACS-sorted inflammasomes, we identify a protein complex modulating inflammasome activity on endosomes. ZFVYE21, a Rab5 effector, partners with Rubicon and RNF34, forming a "ZRR" complex that is stabilized in a Rab5- and ZFYVE21-dependent manner on early endosomes. There, Rubicon competitively disrupts inhibitory associations between caspase-1 and its pseudosubstrate, Flightless I (FliI), while RNF34 ubiquitinylates and degradatively removes FliI from the signaling endosome. The concerted actions of the ZRR complex increase pools of endosome-associated caspase-1 available for activation. The ZRR complex is assembled in human tissues, its associated signaling responses occur in three mouse models in vivo, and the ZRR complex promotes inflammation in a skin model of chronic rejection. The ZRR signaling complex reflects a potential therapeutic target for attenuating inflammasome-mediated tissue injury.

Indexed as

Endothelial CellsInflammasomesAnimalsAntibodiesCarrier ProteinsCaspase 1EndosomesHumansInflammationMiceMicrofilament ProteinsTrans-ActivatorsAntibodiesCarrier ProteinsCaspase 1FlII protein, mouseInflammasomesMicrofilament ProteinsRNF34 protein, humanTrans-Activators

Identifiers

PMID37225719
PMCPMC10209169
OpenAlexW4378070498

What OpenQuestion holds

Textmetadata
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.