Evidence map›Paper›PMID 38886581›Full record

ArticleThe EMBO journal2024

Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions.

Keiichiro Tanaka, Minghao Chen, Andrew Prendergast, Zhenwu Zhuang, Ali Nasiri, Divyesh Joshi, Jared Hintzen, Minhwan Chung, Abhishek Kumar, Arya Mani and 4 more

Abstract read
In one paragraph

Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Adhesion G protein-coupled receptors.Pharmacological reviews · 2026
    Review
  5. Article
  6. EndothelialThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
  7. Article
  8. Review
  9. Vascular Mechanobiology: From Membrane to Nucleus.Advances in experimental medicine and biology · 2026
    Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Keiichiro Tanaka *Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, 06511, USA. keiichiro.tanaka@yale.edu.ORCID http://orcid.org/0000-0001-6328-1485
Minghao Chen *Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, 06511, USA.ORCID http://orcid.org/0000-0001-7719-3961
Andrew PrendergastYale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, 06511, USA.
Zhenwu ZhuangYale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, 06511, USA.
Ali NasiriDepartment of Internal Medicine, Yale University, New Haven, CT, USA.
Divyesh JoshiYale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, 06511, USA.ORCID http://orcid.org/0000-0002-4415-2677
Jared HintzenYale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, 06511, USA.
Minhwan ChungYale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, 06511, USA.ORCID http://orcid.org/0000-0001-6720-7514
Abhishek KumarYale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, 06511, USA.ORCID http://orcid.org/0000-0003-3235-1916
Arya ManiYale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, 06511, USA.
Anthony KoleskeDepartment of Molecular Biochemistry and Biophysics, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-4105-9909
Jason CrawfordDepartment of Chemistry, Yale University, New Haven, CT, USA.
Stefania NicoliYale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, 06511, USA.
Martin A SchwartzYale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, 06511, USA. martin.schwartz@yale.edu.ORCID http://orcid.org/0000-0002-2071-1243

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
Integrins in the Endothelial Response to Fluid Shear StressR01HL075092 · NHLBI · YALE UNIVERSITY · PI SCHWARTZ, MARTIN A · 2004 to 2019
$5.1M
The characterization of Cela2a, a novel disease gene for metabolic syndrome in health and diseasesR01DK134329 · NIDDK · YALE UNIVERSITY · PI Arya Mani · 2023 to 2026
$2.6M
The transcriptional regulation of smooth muscle genes by PRDM6 in vascular health and diseasesR01HL171054 · NHLBI · YALE UNIVERSITY · PI Arya Mani · 2024 to 2026
$2.5M
Integrating miR-107 into signaling pathways that coordinate neurogenesis and brain vascular permeabilityR01HL130246 · NHLBI · YALE UNIVERSITY · PI NICOLI, STEFANIA · 2016 to 2020
$2.1M
Foundation for the National Institutes of Health (FNIH) RO1 HL75092,RO1 HL151469HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) 5R01HL130246-05MEXT | Japan Society for the Promotion of Science (JSPS) 805NCATS NIH HHS UL1 TR001863NHLBI NIH HHS R01 HL075092NHLBI NIH HHS R01 HL130246NHLBI NIH HHS R01 HL171054NIDDK NIH HHS R01 DK134329
6 · The paper itself

Abstract

Endothelial cell responses to fluid shear stress from blood flow are crucial for vascular development, function, and disease. A complex of PECAM-1, VE-cadherin, VEGF receptors (VEGFRs), and Plexin D1 located at cell-cell junctions mediates many of these events. However, available evidence suggests that another mechanosensor upstream of PECAM-1 initiates signaling. Hypothesizing that GPCR and Gα proteins may serve this role, we performed siRNA screening of Gα subunits and found that Gαi2 and Gαq/11 are required for activation of the junctional complex. We then developed a new activation assay, which showed that these G proteins are activated by flow. We next mapped the Gα residues required for activation and developed an affinity purification method that used this information to identify latrophilin-2 (Lphn2/ADGRL2) as the upstream GPCR. Latrophilin-2 is required for all PECAM-1 downstream events tested. In both mice and zebrafish, latrophilin-2 is required for flow-dependent angiogenesis and artery remodeling. Furthermore, endothelial-specific knockout demonstrates that latrophilin plays a role in flow-dependent artery remodeling. Human genetic data reveal a correlation between the latrophilin-2-encoding Adgrl2 gene and cardiovascular disease. Together, these results define a pathway that connects latrophilin-dependent G protein activation to subsequent endothelial signaling, vascular physiology, and disease.

Indexed as

Intercellular JunctionsMechanotransduction, CellularReceptors, G-Protein-CoupledReceptors, PeptideAnimalsEndothelial CellsHumansHuman Umbilical Vein Endothelial CellsMiceStress, MechanicalZebrafishADGRL2 protein, humanReceptors, G-Protein-CoupledReceptors, PeptideFluid Shear StressG Protein-coupled ReceptorLatrophilinPECAM-1Vascular Development

Identifiers

PMID38886581
PMCPMC11294477

What OpenQuestion holds

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Registered trials

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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.