TY  - JOUR
A1  - Seiradake, Elena
A1  - Toro, Daniel del
A1  - Nagel, Daniel
A1  - Cop, Florian
A1  - Härtl, Ricarda
A1  - Ruff, Tobias
A1  - Seyit-Bremer, Gönül
A1  - Harlos, Karl
A1  - Border, Ellen Clare
A1  - Acker-Palmer, Amparo
A1  - Jones, E. Yvonne
A1  - Klein, Rüdiger
T1  - FLRT structure : balancing repulsion and cell adhesion in cortical and vascular development
T2  - Neuron
N2  - 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.
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/35400
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-354006
SN  - 1097-4199
SN  - 0896-6273
N1  - This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
VL  - 84
IS  - 2
SP  - 370
EP  - 385
PB  - Cell Press
CY  - Cambridge
ER  -