Lu Wen, Ai Heng, Peng Lin, Wang Jie-jie, Zhang Bin, Liu Xiao, Luo Jian-hong
Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
Department of Physiology, Zhejiang Medical College, Hangzhou, Zhejiang 310053, China.
Exp Neurol. 2015 Sep;271:251-8. doi: 10.1016/j.expneurol.2015.06.016. Epub 2015 Jun 17.
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 LTP stimulation in cultured hippocampal neurons nor fear conditioning in adult mice. Taken together, our study identified NMDAR GluN2B S1284 as a novel phosphorylation site regulated by Cdk5 with implication in neuronal ischemia.
N-甲基-D-天冬氨酸受体（NMDARs）在突触以及多种神经疾病（如中风）中起着关键作用。NMDAR亚基在其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，也有人提出Cdk5参与缺血性损伤。在本研究中，我们发现神经元缺血时，Cdk5可调节GluN2B亚基胞质羧基末端的丝氨酸1284。有趣的是，培养的海马神经元中的氧葡萄糖剥夺（OGD）和小鼠的短暂性全脑缺血均会导致S1284处GluN2B的磷酸化水平发生显著变化。然而，在培养的海马神经元的化学性长时程增强（LTP）刺激或成年小鼠的恐惧条件反射中，该位点的磷酸化均未发现明显变化。综上所述，我们的研究确定NMDAR GluN2B S1284是一个由Cdk5调节的新磷酸化位点，与神经元缺血有关。
