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Publication : p75(NTR) mediates ephrin-A reverse signaling required for axon repulsion and mapping.

First Author  Lim YS Year  2008
Journal  Neuron Volume  59
Issue  5 Pages  746-58
PubMed ID  18786358 Mgi Jnum  J:145459
Mgi Id  MGI:3834780 Doi  10.1016/j.neuron.2008.07.032
Citation  Lim YS, et al. (2008) p75(NTR) mediates ephrin-A reverse signaling required for axon repulsion and mapping. Neuron 59(5):746-58
abstractText  Reverse signaling by ephrin-As upon binding EphAs controls axon guidance and mapping. Ephrin-As are GPI-anchored to the membrane, requiring that they complex with transmembrane proteins that transduce their signals. We show that the p75 neurotrophin receptor (NTR) serves this role in retinal axons. p75(NTR) and ephrin-A colocalize within caveolae along retinal axons and form a complex required for Fyn phosphorylation upon binding EphAs, activating a signaling pathway leading to cytoskeletal changes. In vitro, retinal axon repulsion to EphAs by ephrin-A reverse signaling requires p75(NTR), but repulsion to ephrin-As by EphA forward signaling does not. Constitutive and retina-specific p75(NTR) knockout mice have aberrant anterior shifts in retinal axon terminations in superior colliculus, consistent with diminished repellent activity mediated by graded ephrin-A reverse signaling induced by graded collicular EphAs. We conclude that p75(NTR) is a signaling partner for ephrin-As and the ephrin-A- p75(NTR) complex reverse signals to mediate axon repulsion required for guidance and mapping.
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