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- Title
The dynamic nature of netrin-1 and the structural basis for glycosaminoglycan fragment-induced filament formation.
- Authors
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
- Abstract
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.
- Subjects
GLYCOSAMINOGLYCANS; HEPARIN; HEPARAN sulfate proteoglycans; FIBERS; OLIGOSACCHARIDES; CELL migration
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-36692-w