Evidence map›Paper›PMID 39773732›Full record

ArticleCell communication and signaling : CCS2025

Nanoscopy reveals integrin clustering reliant on kindlin-3 but not talin-1.

Yuanyuan Wu, Ziming Cao, Wei Liu, Jason G Cahoon, Kepeng Wang, Penghua Wang, Liang Hu, Yunfeng Chen, Markus Moser, Anthony T Vella and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell communication and signaling : CCS, 2025. 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
–field-weighted citation impact
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.

  1. Review
  2. Structural basis of kindlin-3 in leukocyte adhesion deficiency III.Journal of thrombosis and haemostasis : JTH · 2026
    Article
  3. Article
  4. Review
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

13 authors.

Yuanyuan WuDepartment of Immunology, University of Connecticut School of Medicine, Connecticut, Farmington, 06030, USA.
Ziming CaoDepartment of Immunology, University of Connecticut School of Medicine, Connecticut, Farmington, 06030, USA.
Wei LiuDepartment of Immunology, University of Connecticut School of Medicine, Connecticut, Farmington, 06030, USA.
Jason G CahoonDepartment of Immunology, University of Connecticut School of Medicine, Connecticut, Farmington, 06030, USA.
Kepeng WangDepartment of Immunology, University of Connecticut School of Medicine, Connecticut, Farmington, 06030, USA.
Penghua WangDepartment of Immunology, University of Connecticut School of Medicine, Connecticut, Farmington, 06030, USA.
Liang HuAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Yunfeng ChenDepartment of Biochemistry and Molecular Biology, Department of Pathology, University of Texas Medical Branch, Galveston, Texas, 77555, USA.
Markus MoserInstitute of Experimental Hematology, School of Medicine, Technical University of Munich, 81675, Munich, Germany.
Anthony T VellaDepartment of Immunology, University of Connecticut School of Medicine, Connecticut, Farmington, 06030, USA.
Klaus LeyImmunology Center of Georgia, Augusta University, Augusta, Georgia, 30912, USA.
Lai WenDepartment of Pharmacology, University of Nevada School of Medicine, Reno, Nevada, 89557, USA. lwen@unr.edu.
Zhichao FanDepartment of Immunology, University of Connecticut School of Medicine, Connecticut, Farmington, 06030, USA. zfan@uchc.edu.

Funding

UTMB OAIC Research Education Component (REC)P30AG024832 · NIA · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI JAMES S. GOODWIN, MD, MELISSA M. MORROW · 2005 to 2026
$26.7M
Molecular mechanism and preclinical translation of beta2 integrin auto-inhibition on neutrophil arrest and inflammationR01HL145454 · NHLBI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI FAN, ZHICHAO · 2019 to 2023
$2.1M
Control of regulatory T cells by IL-17 in colorectal cancerR01CA262430 · NCI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI WANG, KEPENG · 2021 to 2025
$1.8M
Molecular regulation of β2 integrin activation in neutrophil adhesion and inflammationR01HL174533 · NHLBI · UNIVERSITY OF NEVADA RENO · PI Lai Wen · 2024 to 2026
$1.7M
Inhibiting biomechanical platelet aggregation to prevent arterial thrombosis without compromising hemostasisR00HL153678 · NHLBI · UNIVERSITY OF TEXAS MED BR GALVESTON · PI CHEN, YUNFENG · 2022 to 2024
$746k
Cystic Fibrosis Foundation 00841I221Deutsche Forschungsgemeinschaft SFB914 TP A01NCI NIH HHS R01 CA262430NHLBI NIH HHS R00 HL153678NHLBI NIH HHS R00-HL153678NHLBI NIH HHS R01 HL145454NHLBI NIH HHS R01-HL145454NHLBI NIH HHS R01 HL174533NIA NIH HHS P30 AG024832NIA NIH HHS P30-AG024832UConn Health Startup fund
6 · The paper itself

Abstract

backgroundNeutrophils are the most abundant leukocytes in human blood, and their recruitment is essential for innate immunity and inflammatory responses. The initial and critical step of neutrophil recruitment is their adhesion to vascular endothelium, which depends on G protein-coupled receptor (GPCR) triggered integrin inside-out signaling that induces β2 integrin activation and clustering on neutrophils. Kindlin-3 and talin-1 are essential regulators for the inside-out signaling induced β2 integrin activation. However, their contribution in the inside-out signaling induced β2 integrin clustering is unclear because conventional assays on integrin clustering are usually performed on adhered cells, where integrin-ligand binding concomitantly induces integrin outside-in signaling.

methodsWe used flow cytometry and quantitative super-resolution stochastic optical reconstruction microscopy (STORM) to quantify β2 integrin activation and clustering, respectively, in kindlin-3 and talin-1 knockout leukocytes. We also tested whether wildtype or Pleckstrin homology (PH) domain deleted kindlin-3 can rescue the kindlin-3 knockout phenotypes.

resultsGPCR-triggered inside-out signaling alone can induce β2 integrin clustering. As expected, both kindlin-3 and talin-1 knockout decreases integrin activation. Interestingly, only kindlin-3 but not talin-1 contributes to integrin clustering in the scenario of inside-out-signaling, wherein a critical role of the PH domain of kindlin-3 was highlighted.

conclusionsSince talin was known to facilitate integrin clustering in outside-in-signaling-involved cells, our finding provides a paradigm shift by suggesting that the molecular mechanisms of integrin clustering upon inside-out signaling and outside-in signaling are different. Our data also contradict the conventional assumption that integrin activation and clustering are tightly inter-connected by showing separated regulation of the two during inside-out signaling. Our study provides a new mechanism that shows kindlin-3 regulates β2 integrin clustering and suggests that integrin clustering should be assessed independently, aside from integrin activation, when studying leukocyte adhesion in inflammatory diseases.

Indexed as

Membrane ProteinsTalinAnimalsCD18 AntigensCell AdhesionCytoskeletal ProteinsHumansIntegrinsMiceNeoplasm ProteinsNeutrophilsReceptors, G-Protein-CoupledSignal TransductionCD18 AntigensCytoskeletal ProteinsFERMT3 protein, humanIntegrinskindlin-3 protein, mouseMembrane ProteinsNeoplasm ProteinsReceptors, G-Protein-CoupledTalinTLN1 protein, humanIntegrin clusteringKindlin-3Neutrophil adhesionSTORMTalin-1β2 integrin

Identifiers

PMID39773732
PMCPMC11707915

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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.