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

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 di...

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Veröffentlicht in:Nature communications 2023-03, Vol.14 (1), p.1226-1226, Article 1226
Hauptverfasser: Meier, Markus, Gupta, Monika, Akgül, Serife, McDougall, Matthew, Imhof, Thomas, Nikodemus, Denise, Reuten, Raphael, Moya-Torres, Aniel, To, Vu, Ferens, Fraser, Heide, Fabian, Padilla-Meier, Gay Pauline, Kukura, Philipp, Huang, Wenming, Gerisch, Birgit, Mörgelin, Matthias, Poole, Kate, Antebi, Adam, Koch, Manuel, Stetefeld, Jörg
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Sprache:eng
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Zusammenfassung: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. In this work, the authors report that heparin oligosaccharides have a significant impact on the highly dynamic behaviour of netrin-1 by inducing hierarchical and distinct super assemblies leading to unique, yet unknown netrin-1 filament formation.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-36692-w