GPC3-Unc5 receptor complex structure and role in cell migration

Akkermans, Onno; Delloye-Bourgeois, Céline; Peregrina, Claudia; Carrasquero-Ordaz, Maria; Kokolaki, Maria; Berbeira-Santana, Miguel; Chavent, Matthieu; Reynaud, Florie; Raj, Ritu; Agirre, Jon; Aksu, Metin; White, Eleanor; Lowe, E.D.; Amar, Dounia Ben; Zaballa, Sofia; Huo, Jiandong; Pakos, Irene; McCubbin, Patrick T. N.; Comoletti, Davide; Owens, Raymond J.; Robinson, Carol V.; Castellani, Valérie; Toro, Daniel del; Seiradake, E.

doi:10.1016/j.cell.2022.09.025

Cited by 17 publications

(11 citation statements)

References 132 publications

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“…1e ), the dependence receptors themselves were not able to bind to glypican-3, with the exception of UNC5B (Supplementary Fig. 1c ) 20 . While NET1ΔC bound HSPGs in the nM range (Fig.…”

Section: Resultsmentioning

confidence: 95%

The dynamic nature of netrin-1 and the structural basis for glycosaminoglycan fragment-induced filament formation

et al. 2023

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Netrin-1 is a bifunctional chemotropic guidance cue that plays key roles in diverse cellular processes including axon pathfinding, cell migration, adhesion, differentiation, and survival. Here, we present a molecular understanding of netrin-1 mediated interactions with glycosaminoglycan chains of diverse heparan sulfate proteoglycans (HSPGs) and short heparin oligosaccharides. Whereas interactions with HSPGs act as platform to co-localise netrin-1 close to the cell surface, heparin oligosaccharides have a significant impact on the highly dynamic behaviour of netrin-1. Remarkably, the monomer-dimer equilibrium of netrin-1 in solution is abolished in the presence of heparin oligosaccharides and replaced with highly hierarchical and distinct super assemblies leading to unique, yet unknown netrin-1 filament formation. In our integrated approach we provide a molecular mechanism for the filament assembly which opens fresh paths towards a molecular understanding of netrin-1 functions.

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“…1e ), the dependence receptors themselves were not able to bind to glypican-3, with the exception of UNC5B (Supplementary Fig. 1c ) 20 . While NET1ΔC bound HSPGs in the nM range (Fig.…”

Section: Resultsmentioning

confidence: 95%

The dynamic nature of netrin-1 and the structural basis for glycosaminoglycan fragment-induced filament formation

et al. 2023

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“…Unc5b, for instance, might be such a candidate, as it is expressed in the dorsal retina 57 and was just recently found to interact in trans with Gpc3. 58 …”

Section: Discussionmentioning

confidence: 99%

Teneurin trans-axonal signaling prunes topographically missorted axons

Spead¹,

Moreland²,

Weaver³

et al. 2023

Cell Reports

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“…One of these functions is related to the formation of synapses, where glypicans are part of critical synapse‐organizing protein complexes 32 . In addition, glypicans are involved in neuron guidance and migration 33 …”

Section: Glypican Functionmentioning

confidence: 99%

“…During the formation of distinct cortical layers in the mouse, Unc5D receptors act as key players in the regulation of neuronal migration. It has been recently shown that GPC3 forms a complex with Unc5D, and that this complex is necessary for the migration of pyramidal neurons in the cortex 33 …”

Section: Glypican Functionmentioning

confidence: 99%

“…It has been recently shown that GPC3 forms a complex with Unc5D, and that this complex is necessary for the migration of pyramidal neurons in the cortex. 33 Glypicans are important regulators of synapse formation. They are part of various synapse-organizing protein complexes, and serve as ligands for G-protein coupled receptor 158 (GPR158), leucine-rich repeat transmembrane neuronal proteins (LRRTMs), and leukocyte common antigen-related (LAR) family receptor protein tyrosine phosphatases (RPTPs).…”

Section: Axon Guidance and Neuron Migrationmentioning

confidence: 99%

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Glypicans, 35 years later

Filmus

2023

Proteoglycan Research

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Glypicans are a family of proteoglycans that are bound to the cell surface by a glycosylphosphatidylinositol anchor. These proteoglycans are highly conserved during evolution, and the mammalian genome contains six members of the family.Glypicans carry two to four heparan sulfate chains that are inserted near the carboxy terminus. The crystal structure reveals a densely packed cylindrical shape that is parallel to the cell surface. The functions of glypicans are mediated by the heparan sulfate chains and/or the core protein. One of the main functions of these proteoglycans is the regulation of the signaling pathways triggered by hedgehogs, Wnts, fibroblast growth factors, and bone morphogenetic proteins. Glypicans can either stimulate or inhibit the interaction of these growth factors with their signaling receptors. Studies in Drosophila have also shown that glypicans can regulate hedgehog, Wnt, and bone morphogenetic factor gradient formation. In addition, glypicans play important roles in the establishment of synapses and in neuron guidance and migration. Glypican mutations cause several developmental syndromes, and overexpression of these proteins contribute to the progression of various cancer types. In particular, glypican-3 is currently being used as a marker for the diagnosis of hepatocellular carcinomas, and it is being targeted by several immunotherapeutic approaches for the treatment of this malignancy.

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GPC3-Unc5 receptor complex structure and role in cell migration

Cited by 17 publications

References 132 publications

The dynamic nature of netrin-1 and the structural basis for glycosaminoglycan fragment-induced filament formation

The dynamic nature of netrin-1 and the structural basis for glycosaminoglycan fragment-induced filament formation

Teneurin trans-axonal signaling prunes topographically missorted axons

Glypicans, 35 years later

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