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Related Experiment Video

Updated: Aug 25, 2025

Imaging G-protein Coupled Receptor GPCR-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum

Imaging G-protein Coupled Receptor GPCR-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum

Published on: September 20, 2011

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

Onno Akkermans¹, Céline Delloye-Bourgeois², Claudia Peregrina³

¹Department of Biochemistry, University of Oxford, Oxford, UK.

|October 14, 2022

Summary

This summary is machine-generated.

This study reveals the structure of Uncoordinated-5 receptor D (Unc5D) bound to glypican-3 (GPC3), uncovering how their interactions guide neural cell migration and cancer cell dissemination.

Keywords:

GPC3 UNC5A UNC5B UNC5C UNC5D Unc5 cell guidance cell migration cortex development crystallography glypican-3 nanobodies neuroblastoma stripe assay structural biology surface plasmon resonance uncoordinated-5

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Ex Vivo Imaging of Postnatal Cerebellar Granule Cell Migration Using Confocal Macroscopy

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Published on: May 12, 2015

Area of Science:

Neuroscience
Structural Biology
Cancer Biology

Background:

Neural migration is crucial for brain development, involving cell-surface guidance receptors.
Cancer cells exploit these developmental mechanisms for metastasis.

Purpose of the Study:

To elucidate the structural basis of Uncoordinated-5 receptor D (Unc5D) and glypican-3 (GPC3) interactions.
To understand the role of Unc5D-GPC3 complexes in cell guidance during development and cancer.

Main Methods:

X-ray crystallography to determine the octameric complex structure.
Molecular dynamics simulations and mass spectrometry for validation.
Structure-based mutagenesis and nanobody assays in mouse and xenograft models.

Main Results:

Crystal structures revealed an octameric Unc5D-GPC3 complex with central glycan-glycan interactions.
N-linked glycans from GPC3 and C-mannosylated tryptophans of Unc5D mediate binding.
Unc5D-GPC3 interactions were shown to guide pyramidal neuron migration and neuroblastoma cell dissemination.

Conclusions:

A conserved structural mechanism for cell guidance mediated by Unc5D-GPC3 interactions was demonstrated.
Finely balanced Unc5D-GPC3 binding is critical for regulating cell migration in both development and disease.