Evidence map›Paper›PMID 36240740›Full record

ArticleCell2022

GPC3-Unc5 receptor complex structure and role in cell migration.

Onno Akkermans, Céline Delloye-Bourgeois, Claudia Peregrina, Maria Carrasquero-Ordaz, Maria Kokolaki, Miguel Berbeira-Santana, Matthieu Chavent, Florie Reynaud, Ritu Raj, Jon Agirre and 14 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.5field-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

28 citing papers in PubMed, 41 citations in OpenAlex.

  1. Glypican-3-targeted bioconjugates for hepatocellular carcinoma: design, engineering, and translational applications.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 9 institutions in 4 countries.

Onno AkkermansDepartment of Biochemistry, University of Oxford, Oxford, UK.
Céline Delloye-BourgeoisMeLis, University of Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5284, INSERM U1314, Institut NeuroMyoGène, 8 avenue Rockefeller 69008 Lyon, Lyon, France.
Claudia PeregrinaDepartment of Biological Sciences, Institute of Neurosciences, IDIBAPS, CIBERNED, University of Barcelona, Barcelona, Spain.
Maria Carrasquero-OrdazDepartment of Biochemistry, University of Oxford, Oxford, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, UK.
Maria KokolakiDepartment of Biochemistry, University of Oxford, Oxford, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, UK.
Miguel Berbeira-SantanaDepartment of Biochemistry, University of Oxford, Oxford, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, UK.
Matthieu ChaventInstitut de Pharmacologie et Biologie Structurale, Université de Toulouse, Toulouse, France.
Florie ReynaudMeLis, University of Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5284, INSERM U1314, Institut NeuroMyoGène, 8 avenue Rockefeller 69008 Lyon, Lyon, France.
Ritu RajDepartment of Chemistry, University of Oxford, Oxford, UK.
Jon AgirreYork Structural Biology Laboratory, Department of Chemistry, University of York, York, UK.
Metin AksuDepartment of Biochemistry, University of Oxford, Oxford, UK.
Eleanor S WhiteDepartment of Biochemistry, University of Oxford, Oxford, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, UK.
Edward LoweDepartment of Biochemistry, University of Oxford, Oxford, UK.
Dounia Ben AmarMeLis, University of Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5284, INSERM U1314, Institut NeuroMyoGène, 8 avenue Rockefeller 69008 Lyon, Lyon, France.
Sofia ZaballaDepartment of Biological Sciences, Institute of Neurosciences, IDIBAPS, CIBERNED, University of Barcelona, Barcelona, Spain.
Jiandong HuoStructural Biology, The Rosalind Franklin Institute, Harwell Science Campus, Didcot, UK; Division of Structural Biology, University of Oxford, Oxford, UK.
Irene PakosChild Health Institute of New Jersey, New Brunswick, NJ 08901, USA.
Patrick T N McCubbinDepartment of Biochemistry, University of Oxford, Oxford, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, UK.
Davide ComolettiChild Health Institute of New Jersey, New Brunswick, NJ 08901, USA; School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
Raymond J OwensStructural Biology, The Rosalind Franklin Institute, Harwell Science Campus, Didcot, UK; Division of Structural Biology, University of Oxford, Oxford, UK.
Carol V RobinsonDepartment of Chemistry, University of Oxford, Oxford, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, UK.
Valérie CastellaniMeLis, University of Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5284, INSERM U1314, Institut NeuroMyoGène, 8 avenue Rockefeller 69008 Lyon, Lyon, France. Electronic address: valerie.castellani@univ-lyon1.fr.
Daniel Del ToroDepartment of Biological Sciences, Institute of Neurosciences, IDIBAPS, CIBERNED, University of Barcelona, Barcelona, Spain. Electronic address: danieldeltoro@ub.edu.
Elena SeiradakeDepartment of Biochemistry, University of Oxford, Oxford, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, UK. Electronic address: elena.seiradake@bioch.ox.ac.uk.
University of Oxford · GBCentre National de la Recherche Scientifique · FRUniversitat de Barcelona · ESConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESInserm · FRInstitut NeuroMyoGène · FRUniversité de Toulouse · FRUniversity of York · GBVictoria University of Wellington · NZ

Funding

Wellcome TrustWellcome Trust 202827/Z/16/Z
6 · The paper itself

Abstract

Neural migration is a critical step during brain development that requires the interactions of cell-surface guidance receptors. Cancer cells often hijack these mechanisms to disseminate. Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein complex. In the complex, four Unc5D molecules pack into an antiparallel bundle, flanked by four GPC3 molecules. Central glycan-glycan interactions are formed by N-linked glycans emanating from GPC3 (N241 in human) and C-mannosylated tryptophans of the Unc5D thrombospondin-like domains. MD simulations, mass spectrometry and structure-based mutants validate the crystallographic data. Anti-GPC3 nanobodies enhance or weaken Unc5-GPC3 binding and, together with mutant proteins, show that Unc5/GPC3 guide migrating pyramidal neurons in the mouse cortex, and cancer cells in an embryonic xenograft neuroblastoma model. The results demonstrate a conserved structural mechanism of cell guidance, where finely balanced Unc5-GPC3 interactions regulate cell migration.

Indexed as

Cell MovementAnimalsGlypicansHumansMiceMutant ProteinsNetrin ReceptorsReceptors, Cell SurfaceSingle-Domain AntibodiesThrombospondinsGlypicansGPC3 protein, humanGPC3 protein, mouseMutant ProteinsNetrin ReceptorsReceptors, Cell SurfaceSingle-Domain AntibodiesThrombospondinsUnc5A protein, mouseUnc5b protein, mousecell guidancecell migrationcortex developmentcrystallographyglypican-3GPC3nanobodiesneuroblastomastripe assaystructural biologysurface plasmon resonanceUnc5UNC5AUNC5BUNC5CUNC5Duncoordinated-5

Identifiers

PMID36240740
PMCPMC9596381
OpenAlexW4305015942

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.