FLRT structure : balancing repulsion and cell adhesion in cortical and vascular development

  • FLRTs are broadly expressed proteins with the unique property of acting as homophilic cell adhesion molecules and as heterophilic repulsive ligands of Unc5/Netrin receptors. How these functions direct cell behavior and the molecular mechanisms involved remain largely unclear. Here we use X-ray crystallography to reveal the distinct structural bases for FLRT-mediated cell adhesion and repulsion in neurons. We apply this knowledge to elucidate FLRT functions during cortical development. We show that FLRTs regulate both the radial migration of pyramidal neurons, as well as their tangential spread. Mechanistically, radial migration is controlled by repulsive FLRT2-Unc5D interactions, while spatial organization in the tangential axis involves adhesive FLRT-FLRT interactions. Further, we show that the fundamental mechanisms of FLRT adhesion and repulsion are conserved between neurons and vascular endothelial cells. Our results reveal FLRTs as powerful guidance factors with structurally encoded repulsive and adhesive surfaces.

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Author:Elena Seiradake, Daniel del Toro, Daniel Nagel, Florian Cop, Ricarda Härtl, Tobias Ruff, Gönül Seyit-Bremer, Karl Harlos, Ellen Clare Border, Amparo Acker-PalmerORCiDGND, E. Yvonne Jones, Rüdiger Klein
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/25374360
Parent Title (English):Neuron
Publisher:Cell Press
Place of publication:Cambridge
Document Type:Article
Year of Completion:2014
Date of first Publication:2014/10/22
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2014/10/28
Page Number:40
First Page:370
Last Page:385
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
Institutes:Biowissenschaften / Biowissenschaften
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlung Biologie / Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell-Keine Bearbeitung 3.0