Evidence map›Paper›PMID 33740419›Full record

ArticleCell2021

Simultaneous binding of Guidance Cues NET1 and RGM blocks extracellular NEO1 signaling.

Ross A Robinson, Samuel C Griffiths, Lieke L van de Haar, Tomas Malinauskas, Eljo Y van Battum, Pavol Zelina, Rebekka A Schwab, Dimple Karia, Lina Malinauskaite, Sara Brignani and 9 more

Open access · hybridAbstract read
In one paragraph

Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.9field-weighted citation impact, top 8% 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

32 citing papers in PubMed, 41 citations in OpenAlex.

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  4. Structural Insights into Ordered Multicomponent Assemblies in Cell Junctions.Advances in experimental medicine and biology · 2026
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  16. VWD domain stabilization by autocatalytic Asp-Pro cleavage.Protein science : a publication of the Protein Society · 2024
    Article
  17. Article
  18. Article
  19. Review
  20. 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

19 authors at 5 institutions in 2 countries.

Ross A RobinsonDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Samuel C GriffithsDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Lieke L van de HaarDepartment of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
Tomas MalinauskasDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Eljo Y van BattumDepartment of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
Pavol ZelinaDepartment of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
Rebekka A SchwabDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Dimple KariaDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Lina MalinauskaiteMRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Sara BrignaniDepartment of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
Marleen H van den MunkhofDepartment of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
Özge DüdükcüDepartment of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
Anna A De RuiterDepartment of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
Dianne M A Van den HeuvelDepartment of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
Benjamin BishopDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Jonathan ElegheertDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
A Radu AricescuDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK; MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK.
R Jeroen PasterkampDepartment of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands. Electronic address: r.j.pasterkamp@umcutrecht.nl.
Christian SieboldDivision of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK. Electronic address: christian@strubi.ox.ac.uk.
Centre for Human Genetics · GBUniversity Medical Center Utrecht · NLUtrecht University · NLMRC Laboratory of Molecular Biology · GBUniversity of Oxford · GB

Funding

Cancer Research UK 14414Cancer Research UK 26752Cancer Research UK C20724/A14414Cancer Research UK C20724/A26752Medical Research Council MC_EX_MR/L009609/2Medical Research Council MC_PC_17137Medical Research Council MC_UP_1201/15Medical Research Council MR/L009609/1Medical Research Council MR/L017776/1Wellcome TrustWellcome Trust MC_UP_1201/15
6 · The paper itself

Abstract

During cell migration or differentiation, cell surface receptors are simultaneously exposed to different ligands. However, it is often unclear how these extracellular signals are integrated. Neogenin (NEO1) acts as an attractive guidance receptor when the Netrin-1 (NET1) ligand binds, but it mediates repulsion via repulsive guidance molecule (RGM) ligands. Here, we show that signal integration occurs through the formation of a ternary NEO1-NET1-RGM complex, which triggers reciprocal silencing of downstream signaling. Our NEO1-NET1-RGM structures reveal a "trimer-of-trimers" super-assembly, which exists in the cell membrane. Super-assembly formation results in inhibition of RGMA-NEO1-mediated growth cone collapse and RGMA- or NET1-NEO1-mediated neuron migration, by preventing formation of signaling-compatible RGM-NEO1 complexes and NET1-induced NEO1 ectodomain clustering. These results illustrate how simultaneous binding of ligands with opposing functions, to a single receptor, does not lead to competition for binding, but to formation of a super-complex that diminishes their functional outputs.

Indexed as

AnimalsCell Adhesion Molecules, NeuronalCell MovementDCC ReceptorGPI-Linked ProteinsGrowth ConesHumansLateral VentriclesMiceMice, Inbred C57BLMice, KnockoutNerve Tissue ProteinsNeuronsOncogene ProteinsProtein BindingProtein MultimerizationCell Adhesion Molecules, NeuronalDcc protein, mouseDCC ReceptorGPI-Linked ProteinsNerve Tissue ProteinsNET1 protein, humanOncogene ProteinsRGMA protein, humanRGMB protein, humanRNA, Small Interferingaxon regenerationcell migrationcell surface receptorscomplex structuremorphogen signalingNeogeninNetrinprotein-protein interactionsrepulsive guidance moleculesignal transduction

Identifiers

PMID33740419
PMCPMC8063088
OpenAlexW3138631549

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.