A novel phosphorylation site of N-methyl-D-aspartate receptor GluN2B at S1284 is regulated by Cdk5 in neuronal ischemia
A novel phosphorylation site of N-methyl-D-aspartate receptor GluN2B at S1284 is regulated by Cdk5 in neuronal ischemia
复制标题
N-甲基-d-天冬氨酸受体 GluN2B 在 S1284 上的一个新磷酸化位点在神经元缺血中受 Cdk5 调节。
DOI：
10.1016/j.expneurol.2015.06.016
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发表时间：
2015-09-01
影响因子：
5.3
通讯作者：
Luo, Jian-hong
中科院分区：
文献类型：
--
作者：
Lu, Wen;Ai, Heng;Luo, Jian-hong
n -甲基- d -天冬氨酸受体（NMDARs）在突触和一些神经系统疾病（如中风）中起着关键作用。NMDAR亚基胞质羧基末端的磷酸化被认为是调节受体功能的重要机制。细胞周期蛋白依赖性激酶5 （Cdk5）已被证明负责调节NMDARs的磷酸化和功能。此外，Cdk5还参与了缺血损伤。本研究发现，GluN2B胞质羧基末端的1284丝氨酸在神经元缺血中受Cdk5的调控。有趣的是，培养海马神经元的氧葡萄糖剥夺（OGD）和小鼠的短暂性全脑缺血都会引起S1284处GluN2B磷酸化水平的剧烈变化。然而，无论是在培养海马神经元的化学LW刺激中，还是在成年小鼠的恐惧条件反射中，都没有发现该位点磷酸化的显著变化。综上所述，我们的研究发现NMDAR GluN2B S1284是一个受Cdk5调控的新的磷酸化位点，与神经元缺血有关。(C) 2015 Elsevier Inc .版权所有
N-methyl-D-aspartate receptors (NMDARs) are a key player in synaptic and several neurological diseases, such as stroke. Phosphorylation of NMDAR subunits at their cytoplasmic carboxyl termini has been considered to be an important mechanism to regulate the receptor function. Cyclin-dependent kinase 5 (Cdk5) has been demonstrated to be responsible for regulating phosphorylation and function of NMDARs. Besides, it is also suggested that Cdk5 is involved in ischemic insult In the present study, we showed that GluN2B subunit serine 1284 at its cytoplasmic carboxyl termini was regulated by Cdk5 in neuronal ischemia. Interestingly, both oxygen glucose deprivation (OGD) in cultured hippocampal neurons and transient global ischemia in mice induce dramatic changes in the phosphorylated level of GluN2B at S1284. However, no significant changes in the phosphorylation of this site are found neither in chemical LW stimulation in cultured hippocampal neurons nor fear conditioning in adult mice. Taken together, our study identified NMDAR GluN2B S1284 as a novel phosphoiylation site regulated by Cdk5 with implication in neuronal ischemia. (C) 2015 Elsevier Inc All rights reserved.