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  FLRT Structure: Balancing Repulsion and Cell Adhesion in Cortical and Vascular Development

Seiradake, E., Del Toro Ruiz, D., Nagel, D., Cop, F., Härtl, R., Ruff, T., et al. (2014). FLRT Structure: Balancing Repulsion and Cell Adhesion in Cortical and Vascular Development. NEURON, 84(2), 370-385. doi:10.1016/j.neuron.2014.10.008.

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 Creators:
Seiradake, Elena1, Author
Del Toro Ruiz, Daniel2, Author              
Nagel, Daniel2, Author              
Cop, Florian1, Author
Härtl, Ricarda1, Author
Ruff, Tobias2, Author              
Seyit-Bremer, Gönül2, Author              
Harlos, Karl1, Author
Border, Ellen Clare1, Author
Acker-Palmer, Amparo1, Author
Jones, E. Yvonne1, Author
Klein, Rüdiger3, Author              
Affiliations:
1external, ou_persistent22              
2Department: Molecules-Signaling-Development / Klein, MPI of Neurobiology, Max Planck Society, ou_1113546              
3Department: Molecular Neurobiology / Klein, MPI of Neurobiology, Max Planck Society, ou_1113546              

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Free keywords: INHIBITS SPROUTING ANGIOGENESIS; NERVOUS-SYSTEM; CRYSTAL-STRUCTURE; PROTEIN; UNC5B; RECEPTOR; MIGRATION; EMBRYOS; EXPRESSION; NEURONS
 Abstract: 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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Language(s): eng - English
 Dates: 2014
 Publication Status: Published in print
 Pages: 16
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: NEURON
Source Genre: Journal
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Publ. Info: 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA : CELL PRESS
Pages: - Volume / Issue: 84 (2) Sequence Number: - Start / End Page: 370 - 385 Identifier: ISSN: 0896-6273