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PSD‐95 eliminates Src‐induced potentiation of NR1/NR2A‐subtype NMDA receptor channels and reduces high‐affinity zinc inhibition
Author(s) -
Yamada Yasue,
Iwamoto Takashi,
Watanabe Yoshifumi,
Sobue Kenji,
Inui Makoto
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.00886.x
Subject(s) - long term potentiation , nmda receptor , proto oncogene tyrosine protein kinase src , phosphorylation , microbiology and biotechnology , receptor , biology , chemistry , biophysics , biochemistry
The channel activity of NMDA receptors is regulated by phosphorylation by protein kinases and by interaction with other proteins. Recombinant NR1/NR2A subtype NMDA receptor channels are potentiated by the protein tyrosine kinase Src, an effect which is mediated by a reduction in the high‐affinity, voltage‐independent Zn 2+ inhibition. However, it has been reported that Src‐induced potentiation of NMDA receptor currents in hippocampus neurons is not mediated by a reduction in Zn 2+ inhibition. The post‐synaptic density protein PSD‐95 interacts with the C‐terminus of NR2 subunits of the NMDA receptor. Here we demonstrate that PSD‐95 eliminates the Src‐induced potentiation of NR1/NR2A channels expressed in oocytes and reduces the sensitivity of the channels to Zn 2+ . Our results reveal that the absence of Src‐induced potentiation of PSD‐95‐coupled NR1/NR2A channels is not to due to the reduced sensitivity of these channels to Zn 2+ . These results indicate that PSD‐95 functionally modulates NR1/NR2A channels and explain why Src‐induced potentiation of NMDA receptor currents in hippocampus neurons is not mediated by a reduction in Zn 2+ inhibition.