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


  • M. Meier
  • M. Gupta
  • S. Akgül
  • M. McDougall
  • T. Imhof
  • D. Nikodemus
  • R. Reuten
  • A. Moya-Torres
  • V. To
  • F. Ferens
  • F. Heide
  • G.P. Padilla-Meier
  • P. Kukura
  • W. Huang
  • B. Gerisch
  • M. Mörgelin
  • K. Poole
  • A. Antebi
  • M. Koch
  • J. Stetefeld


  • Nature Communications


  • Nat Commun 14 (1): 1226


  • 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.