EphBs and ephrin-Bs: Trans-synaptic organizers of synapse development and function

Synapses are specialized cell-cell junctions that underlie the function of neural circuits by mediating communication between neurons. Both the formation and function of synapses require tight coordination of signaling between pre- and post-synaptic neurons. Trans-synaptic organizing molecules are important mediators of such signaling. Here we discuss how the EphB and ephrin-B families of trans-synaptic organizing proteins direct synapse formation during early development and regulate synaptic function and plasticity at mature synapses. Finally, we highlight recent evidence linking the synaptic organizing role of EphBs and ephrin-Bs to diseases of maladaptive synaptic function and plasticity. •Trans-synaptic Eph-ephrin interactions coordinate pre- and post-synaptic signaling.•Post-synaptic EphBs regulate synapse and spine formation early in development.•Ephrin-Bs play diverse pre- and post-synaptic roles depending on their localization.•EphBs and ephrin-Bs regulate glutamate receptors and plasticity at mature synapses.•Both too little and too much EphB signaling are involved in CNS diseases.