Dual palmitoylation of NR2 subunits regulates NMDA receptor trafficking.
Dual palmitoylation of NR2 subunits regulates NMDA receptor trafficking.
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DOI：
10.1016/j.neuron.2009.08.017
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发表时间：
2009-10-29
期刊：
影响因子：
16.2
通讯作者：
Huganir, Richard L.
中科院分区：
文献类型：
--
作者：
Hayashi, Takashi;Thomas, Gareth M.;Huganir, Richard L.
NMDA受体功能和运输的修饰有助于调节突触传递，并且对于几种形式的突触可塑性是重要的。在这里，我们报告，NMDA受体亚基NR 2A和NR 2B有两个不同的簇棕榈酰化位点在其C-末端区域。在膜近端区域上的第一簇内的棕榈酰化通过Src家族蛋白酪氨酸激酶增加基于酪氨酸的内化基序的酪氨酸磷酸化，导致NMDA受体的增强的稳定表面表达。此外，这些位点的棕榈酰化调节发育神经元中NMDA受体的组成性内化。与此形成鲜明对比的是，棕榈酰化的第二簇在中间的C-末端由不同的棕榈酰转移酶导致受体聚集在高尔基体，并减少受体表面表达。这些数据表明，调节棕榈酰化的NR 2亚基差异调节受体运输，可能是重要的NMDA受体依赖性突触可塑性。
Modification of NMDA receptor function and trafficking contributes to the regulation of synaptic transmission and is important for several forms of synaptic plasticity. Here, we report that NMDA receptor subunits NR2A and NR2B have two distinct clusters of palmitoylation sites in their C-terminal region. Palmitoylation within the first cluster on a membrane proximal region increases tyrosine phosphorylation of tyrosine-based internalization motifs by Src family protein tyrosine kinases, leading to enhanced stable surface expression of NMDA receptors. In addition, palmitoylation of these sites regulates constitutive internalization of the NMDA receptor in developing neurons. In marked contrast, palmitoylation of the second cluster in the middle of C-terminus by distinct palmitoyl transferases causes receptors to accumulate in the Golgi apparatus and reduces receptor surface expression. These data suggest that regulated palmitoylation of NR2 subunits differentially modulate receptor trafficking and may be important for NMDA receptor dependent synaptic plasticity.
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