奈特林
硫酸乙酰肝素
轴突引导
细胞生物学
糖胺聚糖
蛋白质丝
肝素
化学
生物物理学
生物
生物化学
轴突
作者
Markus Meier,Monika Gupta,Serife Akgül,Matthew McDougall,Thomas Imhof,Denise Nikodemus,Raphael Reuten,Aniel Moya-Torres,Vu To,Fraser G. Ferens,Fabian Heide,G. Pauline Padilla-Meier,Philipp Kukura,Wenming Huang,Birgit Gerisch,Matthias Mörgelin,Kate Poole,Luca Dolfi,Manuel Koch,Jörg Stetefeld
标识
DOI:10.1038/s41467-023-36692-w
摘要
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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