Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses.
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.
Huang
Y Z
YZ
Department of Neurobiology, Pathology, and Physical Medicine and Rehabilitation, University of Alabama at Birmingham, 35294, USA.
Won
S
S
Ali
D W
DW
Wang
Q
Q
Tanowitz
M
M
Du
Q S
QS
Pelkey
K A
KA
Yang
D J
DJ
Xiong
W C
WC
Salter
M W
MW
Mei
L
L
D000818:Animals; D001921:Brain / Q000166:cytology / Q000502:physiology*; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D004558:Electric Stimulation; D066246:ErbB Receptors / Q000378:metabolism / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D017774:Long-Term Potentiation / Q000187:drug effects; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D020880:Neuregulins / Q000494:pharmacology / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D051381:Rats; D066247:Receptor, ErbB-4; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D014018:Tissue Distribution; D015003:Yeasts
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020880:Neuregulins; C033652:postsynaptic density proteins; D066246:ErbB Receptors; C587691:Erbb4 protein, rat; D066247:Receptor, ErbB-4