Anchoring and synaptic stability of PSD-95 is driven by ephrin-B3

PSD-95 is one of the most abundant proteins at synapses and underlies synapse development and function. Hruska and colleagues show that the synaptic localization and turnover of PSD-95 relies on a direct interaction with the trans-synaptic organizer ephrin-B3, which is negatively regulated by neuronal activity through MAPK-dependent phosphorylation of ephrin-B3.