Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNSsynapses

Neuregulins (NRGs) and their receptors, the ErbB protein tyrosine kinases, are essential for neuronal development, but their functions in the adult CN S are unknown. We report that ErbB4 is enriched in the postsynaptic density (PSD) and associates with PSD-95. Heterologous expression of PSD-95 enhanc ed NRG activation of ErbB4 and MAP kinase. Conversely, inhibiting expressio n of PSD-95 in neurons attenuated NRG-mediated activation of MAP kinase. PS D-95 formed a ternary complex with two molecules of ErbB4, suggesting that PSD-95 facilitates ErbB4 dimerization. Finally, NRG suppressed induction of long-term potentiation in the hippocampal CA1 region without affecting bas al synaptic transmission. Thus, NRG signaling may be synaptic and regulated by PSD-95. A role of NRG signaling in the adult CNS may be modulation of s ynaptic plasticity.