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

doi:10.1016/S0896-6273(00)81176-9

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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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 language	English (US)
Pages (from-to)	443-455
Number of pages	13
Journal	Neuron
Volume	26
Issue number	2
DOIs	https://doi.org/10.1016/S0896-6273(00)81176-9
State	Published - 2000

ASJC Scopus subject areas

Neuroscience(all)

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title = "Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses",

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.",

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

note = "Funding Information: We thank Carey Lumeng and Jeff Chamberlain for the cDNA library; Craig Garner, Rick Huganir, Mien-Chie Hung, Lou Kunkel, John Koland, Jacalyn Pierce, Morgan Sheng, Mark Sliwkowski, Mike Weber, and Robert Weinberg for cDNAs and reagents; Hannelore Asmussen and Os Steward for help in neuron culture; Yi Rao for discussion; and Jane Wu for advice. This work is supported by grants from NIH, March of Dimes, MDA, NNSF, and SCST (to L. M.) and by a grant from MRC of Canada (to M. W. S.). M. W. S. is an MRC Scientist; D. W. A. is an MRC fellow, and K. A. P. is the recipient of a studentship from the Savoy Foundation.",

year = "2000",

doi = "10.1016/S0896-6273(00)81176-9",

language = "English (US)",

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pages = "443--455",

journal = "Neuron",

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T1 - Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses

AU - Huang, Yang Z.

AU - Won, Sandra

AU - Ali, Declan W.

AU - Wang, Qiang

AU - Tanowitz, Michael

AU - Du, Quan S.

AU - Pelkey, Kenneth A.

AU - Yang, Da J.

AU - Xiong, Wen C.

AU - Salter, Michael W.

AU - Mei, Lin

N1 - Funding Information: We thank Carey Lumeng and Jeff Chamberlain for the cDNA library; Craig Garner, Rick Huganir, Mien-Chie Hung, Lou Kunkel, John Koland, Jacalyn Pierce, Morgan Sheng, Mark Sliwkowski, Mike Weber, and Robert Weinberg for cDNAs and reagents; Hannelore Asmussen and Os Steward for help in neuron culture; Yi Rao for discussion; and Jane Wu for advice. This work is supported by grants from NIH, March of Dimes, MDA, NNSF, and SCST (to L. M.) and by a grant from MRC of Canada (to M. W. S.). M. W. S. is an MRC Scientist; D. W. A. is an MRC fellow, and K. A. P. is the recipient of a studentship from the Savoy Foundation.

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

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

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