Evidence map›Paper›PMID 30446640›Full record

ArticleNature communications2018

Endothelial cell rearrangements during vascular patterning require PI3-kinase-mediated inhibition of actomyosin contractility.

Ana Angulo-Urarte, Pedro Casado, Sandra D Castillo, Piotr Kobialka, Maria Paraskevi Kotini, Ana M Figueiredo, Pau Castel, Vinothini Rajeeve, Maria Milà-Guasch, Jaime Millan and 11 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
3.4field-weighted citation impact, top 6% 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

46 citing papers in PubMed, 84 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. bioRxiv : the preprint server for biology · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  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

21 authors at 9 institutions in 6 countries.

Ana Angulo-UrarteVascular Signalling Laboratory, ProCURE, Oncobell Program, Institut d´Investigació Biomèdica de Bellvitge (IDIBELL), Gran Via de l'Hospitalet 199, 08908, L´Hospitalet de Llobregat, Barcelona, Spain.
Pedro CasadoCentre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, EC1M 6BQ, UK.ORCID http://orcid.org/0000-0002-4207-9349
Sandra D CastilloVascular Signalling Laboratory, ProCURE, Oncobell Program, Institut d´Investigació Biomèdica de Bellvitge (IDIBELL), Gran Via de l'Hospitalet 199, 08908, L´Hospitalet de Llobregat, Barcelona, Spain.
Piotr KobialkaVascular Signalling Laboratory, ProCURE, Oncobell Program, Institut d´Investigació Biomèdica de Bellvitge (IDIBELL), Gran Via de l'Hospitalet 199, 08908, L´Hospitalet de Llobregat, Barcelona, Spain.
Maria Paraskevi KotiniBiozentrum der Universität Basel, Klingelbergstrasse 50/70, 4056, Basel, Switzerland.
Ana M FigueiredoVascular Signalling Laboratory, ProCURE, Oncobell Program, Institut d´Investigació Biomèdica de Bellvitge (IDIBELL), Gran Via de l'Hospitalet 199, 08908, L´Hospitalet de Llobregat, Barcelona, Spain.
Pau CastelHelen Diller Family Comprehensive Cancer Center, University of California-San Francisco, 1450 3rd Street, San Francisco, CA, 94158, USA.
Vinothini RajeeveCentre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, EC1M 6BQ, UK.
Maria Milà-GuaschVascular Signalling Laboratory, ProCURE, Oncobell Program, Institut d´Investigació Biomèdica de Bellvitge (IDIBELL), Gran Via de l'Hospitalet 199, 08908, L´Hospitalet de Llobregat, Barcelona, Spain.
Jaime MillanCentro de Biología Molecular Severo Ochoa, CSIC-UAM, Calle Nicolás Cabrera, 28049, Madrid, Spain.
Cora WiesnerBiozentrum der Universität Basel, Klingelbergstrasse 50/70, 4056, Basel, Switzerland.
Helena SerraVascular Signalling Laboratory, ProCURE, Oncobell Program, Institut d´Investigació Biomèdica de Bellvitge (IDIBELL), Gran Via de l'Hospitalet 199, 08908, L´Hospitalet de Llobregat, Barcelona, Spain.
Laia MuixiVascular Signalling Laboratory, ProCURE, Oncobell Program, Institut d´Investigació Biomèdica de Bellvitge (IDIBELL), Gran Via de l'Hospitalet 199, 08908, L´Hospitalet de Llobregat, Barcelona, Spain.
Oriol CasanovasTranslation Research Laboratory, ProCURE, Oncobell Program, IDIBELL, Gran Via de l'Hospitalet 199, 08908, L´Hospitalet de Llobregat, Barcelona, Spain.ORCID http://orcid.org/0000-0002-4298-3995
Francesc ViñalsTranslation Research Laboratory, ProCURE, Oncobell Program, IDIBELL, Gran Via de l'Hospitalet 199, 08908, L´Hospitalet de Llobregat, Barcelona, Spain.
Markus AffolterBiozentrum der Universität Basel, Klingelbergstrasse 50/70, 4056, Basel, Switzerland.
Holger GerhardtMax-Delbrueck Center for Molecular Medicine (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany.ORCID http://orcid.org/0000-0002-3030-0384
Stephan HuveneersDepartment of Medical Biochemistry, Amsterdam UMC, University of Amsterdam, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands.
Heinz-Georg BeltingBiozentrum der Universität Basel, Klingelbergstrasse 50/70, 4056, Basel, Switzerland.ORCID http://orcid.org/0000-0002-1538-4364
Pedro R CutillasCentre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, EC1M 6BQ, UK.
Mariona GrauperaVascular Signalling Laboratory, ProCURE, Oncobell Program, Institut d´Investigació Biomèdica de Bellvitge (IDIBELL), Gran Via de l'Hospitalet 199, 08908, L´Hospitalet de Llobregat, Barcelona, Spain. mgraupera@idibell.cat.
Institut d'Investigació Biomédica de Bellvitge · ESUniversity of Basel · CHQueen Mary University of London · GBBellvitge University Hospital · ESAmsterdam University Medical Centers · NLCentro de Biología Molecular Severo Ochoa · ESInstituto de Salud Carlos III · ESMax Delbrück Center · DEUniversity of California, San Francisco · US

Funding

European Research Council 311719
6 · The paper itself

Abstract

Angiogenesis is a dynamic process relying on endothelial cell rearrangements within vascular tubes, yet the underlying mechanisms and functional relevance are poorly understood. Here we show that PI3Kα regulates endothelial cell rearrangements using a combination of a PI3Kα-selective inhibitor and endothelial-specific genetic deletion to abrogate PI3Kα activity during vessel development. Quantitative phosphoproteomics together with detailed cell biology analyses in vivo and in vitro reveal that PI3K signalling prevents NUAK1-dependent phosphorylation of the myosin phosphatase targeting-1 (MYPT1) protein, thereby allowing myosin light chain phosphatase (MLCP) activity and ultimately downregulating actomyosin contractility. Decreased PI3K activity enhances actomyosin contractility and impairs junctional remodelling and stabilization. This leads to overstretched endothelial cells that fail to anastomose properly and form aberrant superimposed layers within the vasculature. Our findings define the PI3K/NUAK1/MYPT1/MLCP axis as a critical pathway to regulate actomyosin contractility in endothelial cells, supporting vascular patterning and expansion through the control of cell rearrangement.

Indexed as

Gene Expression Regulation, DevelopmentalActomyosinAnimalsBody PatterningEmbryo, MammalianEmbryo, NonmammalianGene Expression ProfilingHumansHuman Umbilical Vein Endothelial CellsIntercellular JunctionsLungMiceMice, Inbred C57BLMice, TransgenicMyosin-Light-Chain PhosphataseNeovascularization, PhysiologicActomyosinMyosin-Light-Chain PhosphataseNUAK1 protein, mousePhosphatidylinositol 3-KinasesPhosphoproteinsPpp1r12a protein, mouseProtein KinasesRepressor Proteins

Identifiers

PMID30446640
PMCPMC6240100
OpenAlexW2901217248

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.