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

Yang Z. Huang, Sandra Won, Declan W. Ali, Qiang Wang, Michael Tanowitz, Quan S. Du, Kenneth A. Pelkey, Da J. Yang, Wen C. Xiong, Michael W. Salter, Lin Mei

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298 Scopus citations

Abstract

Neuregulins (NRGs) and their receptors, the ErbB protein tyrosine kinases, are essential for neuronal development, but their functions in the adult CNS are unknown. We report that ErbB4 is enriched in the postsynaptic density (PSD) and associates with PSD-95. Heterologous expression of PSD-95 enhanced NRG activation of ErbB4 and MAP kinase. Conversely, inhibiting expression of PSD-95 in neurons attenuated NRG-mediated activation of MAP kinase. PSD-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 basal 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 synaptic plasticity.

Original languageEnglish (US)
Pages (from-to)443-455
Number of pages13
JournalNeuron
Volume26
Issue number2
DOIs
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Neuroscience(all)

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    Huang, Y. Z., Won, S., Ali, D. W., Wang, Q., Tanowitz, M., Du, Q. S., Pelkey, K. A., Yang, D. J., Xiong, W. C., Salter, M. W., & Mei, L. (2000). Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses. Neuron, 26(2), 443-455. https://doi.org/10.1016/S0896-6273(00)81176-9