Phosphorylation of Tyrosine 1070 at the GluN2B Subunit Is Regulated by Synaptic Activity and Critical for Surface Expression of N-Methyl-d-aspartate (NMDA) Receptors |
| |
| Authors: | Wen Lu Weiqing Fang Jian Li Bin Zhang Qian Yang Xunyi Yan Lin Peng Heng Ai Jie-jie Wang Xiao Liu Jianhong Luo Wei Yang |
| |
| Institution: | From the ‡Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China, ;§Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China, and ;¶Department of Physiology, Zhejiang Medical College, Hangzhou, Zhejiang 310053, China |
| |
| Abstract: | The number and subunit composition of synaptic N-methyl-d-aspartate receptors (NMDARs) play critical roles in synaptic plasticity, learning, and memory and are implicated in neurological disorders. Tyrosine phosphorylation provides a powerful means of regulating NMDAR function, but the underling mechanism remains elusive. In this study we identified a tyrosine site on the GluN2B subunit, Tyr-1070, which was phosphorylated by a proto-oncogene tyrosine-protein (Fyn) kinase and critical for the surface expression of GluN2B-containing NMDARs. The phosphorylation of GluN2B at Tyr-1070 was required for binding of Fyn kinase to GluN2B, which up-regulated the phosphorylation of GluN2B at Tyr-1472. Moreover, our results revealed that the phosphorylation change of GluN2B at Tyr-1070 accompanied the Tyr-1472 phosphorylation and Fyn associated with GluN2B in synaptic plasticity induced by both chemical and contextual fear learning. Taken together, our findings provide a new mechanism for regulating the surface expression of NMDARs with implications for synaptic plasticity. |
| |
| Keywords: | N-methyl-d-aspartate receptor (NMDA receptor NMDAR) phosphotyrosine signaling protein-protein interaction Src synaptic plasticity Fyn GluN2B Tyr-1070 |
|
|
