Ephrin-B3 regulates glutamate receptor signaling at hippocampal synapses

B ephrin-EphB receptor signaling modulates NMDA receptors by inducing tyrosine phosphorylation of NR2 subunits Ephrins and EphB RTKs are localized to postsynaptic compartments in the CM and therefore potentially interact in a non-canonical cis- configuration However it is not known whether cis- configured receptor-ligand signaling is utilized by this class of RTKs and whether this might influence excitatory synapses We found that ablation of ephrin 83 results in an enhancement of the NMDA receptor component of synaptic transmission relative to the AMPA receptor component in CA1 synapses Synaptic AMPA receptor expression is reduced in ephrin-B3 knockout mice and there is a marked enhancement of tyrosine phosphorylation of the NR2B receptor subunit In a reduced system co-expression of ephrin-B3 attenuated EphB2-mediated NR2B tyrosine phosphorylation Moreover phosphorylation of EphB2 was elevated in the hippocampus of ephrin-B3 knockout mice suggesting that regulation of EphB2 activity is lost in these mice Direct activation of EphB RTKs resulted in phosphorylation of NR2B and a potential signaling partner the non-receptor tyrosine kinase Pyk2 Our data suggests that ephrin-B3 limits EphB RTK-mediated phosphorylation of the NR2B subunit through an inhibitory as interaction which is required for the correct function of glutamatergic CA1 synapses (C) 2010 Elsevier Inc All rights reserved