A dual-shaping mechanism for postsynaptic ephrin-B3 as a receptor that sculpts dendrites and synapses

As the neural network becomes wired postsynaptic signaling molecules are thought to control the growth of dendrites and synapses. However, how these molecules are coordinated to sculpt postsynaptic structures is less well understood. We find that ephrin-B3, a transmembrane ligand for Eph receptors, functions postsynaptically as a receptor to transduce reverse signals into developing dendrites of murine hippocampal neurons. Both tyrosine phosphorylation-dependent Grb4 SH2/SH3 adaptor-mediated signals and PDZ domain-dependent signals are required to inhibit dendrite branching, while only PDZ interactions are necessary for spine formation and excitatory synaptic function. Pick1 and syntenin, two PDZ domain proteins, participate with ephrin-B3 in these postsynaptic activities. Pick1 plays a specific role in spine/synapse formation, while syntenin promotes both dendrite pruning and synapse formation to build postsynaptic structures essential for neural circuits. The study thus dissects ephrin-B reverse signaling into three distinct intracellular pathways and protein-protein interactions that mediate the maturation of postsynaptic neurons.