AUC 2022

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Biophysical and Structural characterization of Netrin-1 Complexes
Submitter: Haben Gabir
Authors: Haben Gabir, Monika Gupta, Faride Rafiei, Manuel Koch, Borries Demeler, Jörg Stetefeld
Corresponding Author: Haben Gabir
Title: Biophysical and Structural characterization of Netrin-1 Complexes
Contribution Type: Full Talk
Selected for Presentation Yes
Abstract: Netrin-1 is a chemotropic ligand responsible for the bi-functional regulation of commissural axon migration and direction. Netrin-1 controls the attraction and repulsion of the growing end of axons called growth cones. It does so by binding to several dependence receptors, notably Uncoordinated 5 (Unc5) and Deleted in Colorectal Cancer (DCC). Both proteins act as dependence receptors which signal apoptotic pathways in the absence of Netrin-1. Netrin-1 and DCC complexes form multimeric complexes that include the tip of neurons, growth cones, to migrate toward Netrin-1. In contrast, Unc5 repels growth cone migration by collapsing the growth cone tubulin filaments, silencing Netrin-1 and DCC signalling. Using multiwavelength-AUC coupled with SEC-MALS, SEC-SAXS and BLI, we investigate how the Unc5 can repel migrating neurons from Netrin-1 by inhibiting Netrin-1 and DCC complexes.