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

Author

Listed:
  • Markus Meier

    (University of Manitoba)

  • Monika Gupta

    (University of Manitoba)

  • Serife Akgül

    (Faculty of Medicine and University Hospital Cologne, University of Cologne
    Max Planck Institute for Biology of Ageing)

  • Matthew McDougall

    (University of Manitoba)

  • Thomas Imhof

    (Faculty of Medicine and University Hospital Cologne, University of Cologne)

  • Denise Nikodemus

    (Albert Ludwigs University of Freiburg)

  • Raphael Reuten

    (University of Freiburg
    University of Freiburg)

  • Aniel Moya-Torres

    (University of Manitoba)

  • Vu To

    (University of Manitoba)

  • Fraser Ferens

    (University of Manitoba)

  • Fabian Heide

    (University of Manitoba)

  • Gay Pauline Padilla-Meier

    (University of Manitoba)

  • Philipp Kukura

    (University of Oxford)

  • Wenming Huang

    (Max Planck Institute for Biology of Ageing)

  • Birgit Gerisch

    (Max Planck Institute for Biology of Ageing)

  • Matthias Mörgelin

    (Colzyx AB)

  • Kate Poole

    (Max Delbrück Center for Molecular Medicine
    University of New South Wales)

  • Adam Antebi

    (Max Planck Institute for Biology of Ageing
    University of Cologne)

  • Manuel Koch

    (Faculty of Medicine and University Hospital Cologne, University of Cologne
    Faculty of Medicine and University Hospital Cologne, University of Cologne
    Faculty of Medicine and University Hospital Cologne, University of Cologne)

  • Jörg Stetefeld

    (University of Manitoba)

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.

Suggested Citation

  • Markus Meier & Monika Gupta & Serife Akgül & Matthew McDougall & Thomas Imhof & Denise Nikodemus & Raphael Reuten & Aniel Moya-Torres & Vu To & Fraser Ferens & Fabian Heide & Gay Pauline Padilla-Meier, 2023. "The dynamic nature of netrin-1 and the structural basis for glycosaminoglycan fragment-induced filament formation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36692-w
    DOI: 10.1038/s41467-023-36692-w
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    References listed on IDEAS

    as
    1. Raphael Reuten & Trushar R. Patel & Matthew McDougall & Nicolas Rama & Denise Nikodemus & Benjamin Gibert & Jean-Guy Delcros & Carina Prein & Markus Meier & Stéphanie Metzger & Zhigang Zhou & Jennifer, 2016. "Structural decoding of netrin-4 reveals a regulatory function towards mature basement membranes," Nature Communications, Nature, vol. 7(1), pages 1-17, December.
    2. E. David Leonardo & Lindsay Hinck & Masayuki Masu & Kazuko Keino-Masu & Susan L. Ackerman & Marc Tessier-Lavigne, 1997. "Vertebrate homologues of C. elegans UNC-5 are candidate netrin receptors," Nature, Nature, vol. 386(6627), pages 833-838, April.
    Full references (including those not matched with items on IDEAS)

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