Tyrosine kinase potentiates NMDA receptor currents by reducing tonic zinc inhibition
Tyrosine kinase potentiates NMDA receptor currents by reducing tonic zinc inhibition
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DOI：
10.1038/634
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发表时间：
1998-07
影响因子：
25
通讯作者：
F. Zheng;M. B. Gingrich;S. Traynelis;P. Conn
中科院分区：
文献类型：
--
作者：
F. Zheng;M. B. Gingrich;S. Traynelis;P. Conn
酪氨酸激酶Src的激活增强NMDA受体电流，这被认为是诱导海马长时程增强所必需的。虽然NR 2A亚基的羧基（C）末端结构域含有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，我们提出的证据从NR 1突变体和剪接变异体Src增强NMDA受体电流通过减少紧张性抑制受体组成的NR 1和NR 2A亚基由细胞外锌。使用定点突变，我们已经确定了三个C-末端酪氨酸残基NR 2A所需的Src的锌敏感性的NMDA受体的调制。我们的数据链接两个NMDA受体的调节位点，以前被认为是独立的。
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 mechanism 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.