Zheng F, Gingrich M B, Traynelis S F, Conn P J
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Nat Neurosci. 1998 Jul;1(3):185-91. doi: 10.1038/634.
Activation of the tyrosine kinase Src potentiates NMDA-receptor currents, which is thought to be necessary for induction of hippocampal long-term potentiation. Although the carboxy(C)-terminal domain of the NR2A subunit contains potential tyrosine phosphorylation sites, the mechanisms by which Src modulates synaptic plasticity and NMDA receptor currents is not fully understood. Here we present evidence from NR1 mutants and splice variants that Src potentiates NMDA-receptor currents by reducing the tonic inhibition of receptors composed of NR1 and NR2A subunits by extracellular zinc. Using site-directed mutagenesis, we have identified three C-terminal tyrosine residues of NR2A that are required for Src's modulation of the zinc sensitivity of NMDA receptors. Our data link two modulatory sites of NMDA receptors that were previously thought to be independent.
酪氨酸激酶Src的激活增强了NMDA受体电流，这被认为是诱导海马体长期增强所必需的。尽管NR2A亚基的羧基（C）末端结构域包含潜在的酪氨酸磷酸化位点，但Src调节突触可塑性和NMDA受体电流的机制尚未完全了解。在这里，我们提供了来自NR1突变体和剪接变体的证据，表明Src通过减少细胞外锌对由NR1和NR2A亚基组成的受体的强直性抑制来增强NMDA受体电流。使用定点诱变，我们确定了NR2A的三个C末端酪氨酸残基，它们是Src调节NMDA受体锌敏感性所必需的。我们的数据将以前认为是独立的NMDA受体的两个调节位点联系起来。
