4v2a
human Unc5A ectodomainhuman Unc5A ectodomain
Structural highlights
FunctionUNC5A_HUMAN Receptor for netrin required for axon guidance. Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding. Axon repulsion in growth cones may be caused by its association with DCC that may trigger signaling for repulsion. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand. Publication Abstract from PubMedFLRTs 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. FLRT structure: balancing repulsion and cell adhesion in cortical and vascular development.,Seiradake E, del Toro D, Nagel D, Cop F, Hartl R, Ruff T, Seyit-Bremer G, Harlos K, Border EC, Acker-Palmer A, Jones EY, Klein R Neuron. 2014 Oct 22;84(2):370-85. doi: 10.1016/j.neuron.2014.10.008. Epub 2014, Oct 22. PMID:25374360[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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