Evidence map›Paper›PMID 32347571›Full record

ArticleThe EMBO journal2020

RhoJ integrates attractive and repulsive cues in directional migration of endothelial cells.

Yoko Fukushima, Koichi Nishiyama, Hiroshi Kataoka, Marcus Fruttiger, Shigetomo Fukuhara, Kohji Nishida, Naoki Mochizuki, Hiroki Kurihara, Shin-Ichi Nishikawa, Akiyoshi Uemura

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

22 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Article
  3. Decoding Rho GTPase signalling networks in directed cell migration.Frontiers in cell and developmental biology · 2026
    Review
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  5. Article
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  7. Article
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  9. Review
  10. Oncogenic Gαq activates RhoJ through PDZ-RhoGEF.International journal of molecular sciences · 2023
    Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Rho GTPases in Retinal Vascular Diseases.International journal of molecular sciences · 2021
    Review
  19. Review
  20. Article
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

10 authors at 9 institutions in 2 countries.

Yoko FukushimaDivision of Vascular Biology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
Koichi NishiyamaInternational Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan.
Hiroshi KataokaLaboratory for Stem Cell Biology, RIKEN Center for Developmental Biology, Kobe, Japan.
Marcus FruttigerUCL Institute of Ophthalmology, University College London, London, UK.
Shigetomo FukuharaDepartment of Molecular Pathophysiology, Institute for Advanced Medical Sciences, Nippon Medical School, Kawasaki, Japan.
Kohji NishidaDepartment of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan.
Naoki MochizukiDepartment of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
Hiroki KuriharaDepartment of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Shin-Ichi NishikawaLaboratory for Stem Cell Biology, RIKEN Center for Developmental Biology, Kobe, Japan.
Akiyoshi UemuraDivision of Vascular Biology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe, Japan.ORCID 0000-0001-5574-5470
RIKEN Center for Computational Science · JPKobe University · JPKumamoto Medical Center · JPNagoya City University · JPNational Cerebral and Cardiovascular Center · JPNippon Medical School · JPThe University of Osaka · JPThe University of Tokyo · JPUniversity College London · GB

Funding

Eye Research Foundation for the AgedMEXT|Japan Society for the Promotion of Science (JSPS) 16H05155MEXT|Japan Society for the Promotion of Science (JSPS) 16K15737MEXT|Japan Society for the Promotion of Science (JSPS) 19H03437MEXT|Japan Society for the Promotion of Science (JSPS) 25293078MEXT|JST|Core Research for Evolutional Science and Technology (CREST) JPMJCR14W4Takeda Science Foundation
6 · The paper itself

Abstract

During angiogenesis, VEGF acts as an attractive cue for endothelial cells (ECs), while Sema3E mediates repulsive cues. Here, we show that the small GTPase RhoJ integrates these opposing signals in directional EC migration. In the GTP-bound state, RhoJ interacts with the cytoplasmic domain of PlexinD1. Upon Sema3E stimulation, RhoJ released from PlexinD1 induces cell contraction. PlexinD1-bound RhoJ further facilitates Sema3E-induced PlexinD1-VEGFR2 association, VEGFR2 transphosphorylation at Y1214, and p38 MAPK activation, leading to reverse EC migration. Upon VEGF stimulation, RhoJ is required for the formation of the holoreceptor complex comprising VEGFR2, PlexinD1, and neuropilin-1, thereby preventing degradation of internalized VEGFR2, prolonging downstream signal transductions via PLCγ, Erk, and Akt, and promoting forward EC migration. After conversion to the GDP-bound state, RhoJ shifts from PlexinD1 to VEGFR2, which then terminates the VEGFR2 signals. RhoJ deficiency in ECs efficiently suppressed aberrant angiogenesis in ischemic retina. These findings suggest that distinct Rho GTPases may act as context-dependent integrators of chemotactic cues in directional cell migration and may serve as candidate therapeutic targets to manipulate cell motility in disease or tissue regeneration.

Indexed as

Cell MovementSignal TransductionAnimalsEndothelial CellsHumansHuman Umbilical Vein Endothelial CellsIntracellular Signaling Peptides and ProteinsMembrane GlycoproteinsMiceMice, Transgenicrho GTP-Binding ProteinsVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Intracellular Signaling Peptides and ProteinsKDR protein, humanKdr protein, mouseMembrane GlycoproteinsPLXND1 protein, humanPlxnd1 protein, mouserho GTP-Binding ProteinsRHOJ protein, humanRhoj protein, mouseVascular Endothelial Growth Factor Avascular endothelial growth factor A, mouseVascular Endothelial Growth Factor Receptor-2VEGFA protein, humandirectional cell migrationendothelial cellRhoJSema3EVEGF

Identifiers

PMID32347571
PMCPMC7298304
OpenAlexW3019408971

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.