Structural decoding of netrin-4 reveals a regulatory function towards mature basement membranes

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dc.contributor.authorReuten, Raphael
dc.contributor.authorPatel, Trushar R.
dc.contributor.authorMcDougall, Matthew
dc.contributor.authorRama, Nicolas
dc.contributor.authorNikodemus, Denise
dc.contributor.authorGibert, Benjamin
dc.contributor.authorDelcros, Jean-Guy
dc.contributor.authorPrein, Carina
dc.contributor.authorMeier, Markus
dc.contributor.authorMetzger, Stéphanie
dc.contributor.authorZhou, Zhigang
dc.contributor.authorKaltenberg, Jennifer
dc.contributor.authorMcKee, Karen K.
dc.contributor.authorBald, Tobias
dc.contributor.authorTuting, Thomas
dc.contributor.authorZigrino, Paola
dc.contributor.authorDjonov, Valentin
dc.contributor.authorBloch, Wilhelm
dc.contributor.authorClausen-Schaumann, Hauke
dc.contributor.authorPoschl, Ernst
dc.contributor.authorYurchenco, Peter D.
dc.contributor.authorEhrbar, Martin
dc.contributor.authorMehlen, Patrick
dc.contributor.authorStetefeld, Jorg
dc.contributor.authorKoch, Manuel
dc.date.accessioned2024-06-20T20:46:25Z
dc.date.available2024-06-20T20:46:25Z
dc.date.issued2016
dc.descriptionOpen access article. Creative Commons Attribution 4.0 International license (CC BY 4.0) applies
dc.description.abstractNetrins, a family of laminin-related molecules, have been proposed to act as guidance cues either during nervous system development or the establishment of the vascular system. This was clearly demonstrated for netrin-1 via its interaction with the receptors DCC and UNC5s. However, mainly based on shared homologies with netrin-1, netrin-4 was also proposed to play a role in neuronal outgrowth and developmental/pathological angiogenesis via interactions with netrin-1 receptors. Here, we present the high-resolution structure of netrin-4, which shows unique features in comparison with netrin-1, and show that it does not bind directly to any of the known netrin-1 receptors. We show that netrin-4 disrupts laminin networks and basement membranes (BMs) through high-affinity binding to the laminin γ1 chain. We hypothesize that this laminin-related function is essential for the previously described effects on axon growth promotion and angiogenesis. Our study unveils netrin-4 as a non-enzymatic extracellular matrix protein actively disrupting pre-existing BMs.
dc.identifier.citationReuten, R., Patel, T. R., McDougall, M., Rama, N., Nikodemus, D., Gibert, B., Delcros, J.-G., Prein, C., Meier, M., Metzger, S., Zhou, Z., Kaltenberg, J., McKee, K. K., Bald, T., Tuting, T., Zigrino, P., Djonov, V., Bloch, W., Clausen-Schaumann, H., Poschl, E.,...Koch, M. (2016). Structural decoding of netrin-4 reveals a regulatory function towards mature basement membranes. Nature Communications, 7, Article 13515. https://doi.org/10.1038/ncomms13515
dc.identifier.urihttps://hdl.handle.net/10133/6793
dc.language.isoen
dc.publisherNature Portfolio
dc.publisher.departmentDepartment of Chemistry and Biochemistry
dc.publisher.facultyArts and Science
dc.publisher.institutionUniversity of Cologne
dc.publisher.institutionUniversity of Lethbridge
dc.publisher.institutionUniversity of Birmingham
dc.publisher.institutionUniversity of Manitoba
dc.publisher.institutionUniversité de Lyon
dc.publisher.institutionMunich University
dc.publisher.institutionCenter for Nanoscience-CeNS
dc.publisher.institutionUniversity Hospital Zurich
dc.publisher.institutionUniversity of East Anglia
dc.publisher.institutionRobert Wood Johnson Medical School
dc.publisher.institutionUniversity Hospital Magdeburg
dc.publisher.institutionUniversity of Bonn
dc.publisher.institutionUniversity of Bern
dc.publisher.institutionGerman Sport University Cologne
dc.subjectAxon and dendritic guidance
dc.subjectExtracellular matrix
dc.subjectX-ray crystallography
dc.subjectNetrins
dc.subjectNetrin-4
dc.titleStructural decoding of netrin-4 reveals a regulatory function towards mature basement membranes
dc.typeArticle
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