Evidence map›Paper›PMID 19175293›Full record

ArticlePLoS biology2009

Neuropilin-1/GIPC1 signaling regulates alpha5beta1 integrin traffic and function in endothelial cells.

Donatella Valdembri, Patrick T Caswell, Kurt I Anderson, Juliane P Schwarz, Ireen König, Elena Astanina, Francesca Caccavari, Jim C Norman, Martin J Humphries, Federico Bussolino and 1 more

RetractedOpen access · goldAbstract read
In one paragraph

Article in PLoS biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 162 papers.

0numbers the graph read from it
0cells of the map it votes in
162citing papers in PubMed
9.9field-weighted citation impact, top 1% 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

162 citing papers in PubMed, 269 citations in OpenAlex.

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102 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

Donatella ValdembriDepartment of Oncological Sciences and Division of Molecular Angiogenesis, Institute for Cancer Research and Treatment, University of Torino School of Medicine, Candiolo, Italy.
Patrick T Caswell
Kurt I Anderson
Juliane P Schwarz
Ireen König
Elena Astanina
Francesca Caccavari
Jim C Norman
Martin J Humphries
Federico Bussolino
Guido Serini
Cancer Research UK Scotland Institute · GBCandiolo Cancer Institute · ITUniversity of Turin · ITWellcome Centre for Cell-Matrix Research · GB

Funding

Telethon GGP04127Wellcome Trust
6 · The paper itself

Abstract

Neuropilin 1 (Nrp1) is a coreceptor for vascular endothelial growth factor A165 (VEGF-A165, VEGF-A164 in mice) and semaphorin 3A (SEMA3A). Nevertheless, Nrp1 null embryos display vascular defects that differ from those of mice lacking either VEGF-A164 or Sema3A proteins. Furthermore, it has been recently reported that Nrp1 is required for endothelial cell (EC) response to both VEGF-A165 and VEGF-A121 isoforms, the latter being incapable of binding Nrp1 on the EC surface. Taken together, these data suggest that the vascular phenotype caused by the loss of Nrp1 could be due to a VEGF-A164/SEMA3A-independent function of Nrp1 in ECs, such as adhesion to the extracellular matrix. By using RNA interference and rescue with wild-type and mutant constructs, we show here that Nrp1 through its cytoplasmic SEA motif and independently of VEGF-A165 and SEMA3A specifically promotes alpha5beta1-integrin-mediated EC adhesion to fibronectin that is crucial for vascular development. We provide evidence that Nrp1, while not directly mediating cell spreading on fibronectin, interacts with alpha5beta1 at adhesion sites. Binding of the homomultimeric endocytic adaptor GAIP interacting protein C terminus, member 1 (GIPC1), to the SEA motif of Nrp1 selectively stimulates the internalization of active alpha5beta1 in Rab5-positive early endosomes. Accordingly, GIPC1, which also interacts with alpha5beta1, and the associated motor myosin VI (Myo6) support active alpha5beta1 endocytosis and EC adhesion to fibronectin. In conclusion, we propose that Nrp1, in addition to and independently of its role as coreceptor for VEGF-A165 and SEMA3A, stimulates through its cytoplasmic domain the spreading of ECs on fibronectin by increasing the Rab5/GIPC1/Myo6-dependent internalization of active alpha5beta1. Nrp1 modulation of alpha5beta1 integrin function can play a causal role in the generation of angiogenesis defects observed in Nrp1 null mice.

Indexed as

Signal TransductionAdaptor Proteins, Signal TransducingAnimalsCarrier ProteinsCell AdhesionEndothelium, VascularFibronectinsHumansIntegrin alpha5beta1MiceMice, KnockoutNeovascularization, PhysiologicNeuropeptidesNeuropilin-1Protein BindingRNA InterferenceAdaptor Proteins, Signal TransducingCarrier ProteinsFibronectinsGipc1 protein, mouseIntegrin alpha5beta1NeuropeptidesNeuropilin-1RNA, Small Interfering

Identifiers

PMID19175293
PMCPMC2631072
OpenAlexW2042952122

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.