Receptor Biology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Neuron. 2010 Sep 23;67(6):984-96. doi: 10.1016/j.neuron.2010.08.011.
N-methyl-D-aspartate (NMDA) receptors (NMDARs) play a central role in development, synaptic plasticity, and neurological disease. NMDAR subunit composition defines their biophysical properties and downstream signaling. Casein kinase 2 (CK2) phosphorylates the NR2B subunit within its PDZ-binding domain; however, the consequences for NMDAR localization and function are unclear. Here we show that CK2 phosphorylation of NR2B regulates synaptic NR2B and NR2A in response to activity. We find that CK2 phosphorylates NR2B, but not NR2A, to drive NR2B-endocytosis and remove NR2B from synapses resulting in an increase in synaptic NR2A expression. During development there is an activity-dependent switch from NR2B to NR2A at cortical synapses. We observe an increase in CK2 expression and NR2B phosphorylation over this same critical period and show that the acute activity-dependent switch in NR2 subunit composition at developing hippocampal synapses requires CK2 activity. Thus, CK2 plays a central role in determining the NR2 subunit content of synaptic NMDARs.
N-甲基-D-天冬氨酸（NMDA）受体（NMDARs）在发育、突触可塑性和神经疾病中发挥着核心作用。NMDAR 亚基组成决定了它们的生物物理特性和下游信号转导。酪蛋白激酶 2（CK2）在其 PDZ 结合域内磷酸化 NR2B 亚基；然而，对于 NMDAR 定位和功能的后果尚不清楚。在这里，我们表明 CK2 磷酸化 NR2B 调节突触 NR2B 和 NR2A 对活性的反应。我们发现 CK2 磷酸化 NR2B，但不磷酸化 NR2A，以驱动 NR2B 内吞作用并将 NR2B 从突触中去除，从而导致突触 NR2A 表达增加。在发育过程中，皮质突触上的 NR2B 向 NR2A 的活性依赖性转换。在同一关键时期，我们观察到 CK2 表达和 NR2B 磷酸化的增加，并表明发育中的海马突触中 NR2 亚基组成的急性活性依赖性转换需要 CK2 活性。因此，CK2 在决定突触 NMDA 受体的 NR2 亚基含量方面发挥着核心作用。
