1. Protein Kinase C Promotes N-Methyl-d-aspartate (NMDA) Receptor Trafficking by Indirectly Triggering Calcium/Calmodulin-dependent Protein Kinase II (CaMKII) Autophosphorylation
- Author
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Bin Hu, Zhuo Xu, Jing-Zhi Yan, Wen Yao, Su-Yi Liu, Si-Qiang Ren, Shan-Hui Wang, and Wei Lu
- Subjects
Male ,Long-Term Potentiation ,Synaptic Membranes ,AMPA receptor ,Biology ,Receptors, N-Methyl-D-Aspartate ,Biochemistry ,Rats, Sprague-Dawley ,Neurobiology ,Ca2+/calmodulin-dependent protein kinase ,mental disorders ,Animals ,Phosphorylation ,Molecular Biology ,Protein Kinase C ,Protein kinase C ,musculoskeletal, neural, and ocular physiology ,Autophosphorylation ,Long-term potentiation ,Cell Biology ,Rats ,Cell biology ,Enzyme Activation ,Protein Transport ,nervous system ,Synaptic plasticity ,NMDA receptor ,biological phenomena, cell phenomena, and immunity ,Signal transduction ,Calcium-Calmodulin-Dependent Protein Kinase Type 2 ,psychological phenomena and processes ,Signal Transduction - Abstract
Regulation of neuronal NMDA receptor (NMDAR) is critical in synaptic transmission and plasticity. Protein kinase C (PKC) promotes NMDAR trafficking to the cell surface via interaction with NMDAR-associated proteins (NAPs). Little is known, however, about the NAPs that are critical to PKC-induced NMDAR trafficking. Here, we showed that calcium/calmodulin-dependent protein kinase II (CaMKII) could be a NAP that mediates the potentiation of NMDAR trafficking by PKC. PKC activation promoted the level of autophosphorylated CaMKII and increased association with NMDARs, accompanied by functional NMDAR insertion, at postsynaptic sites. This potentiation, along with PKC-induced long term potentiation of the AMPA receptor-mediated response, was abolished by CaMKII antagonist or by disturbing the interaction between CaMKII and NR2A or NR2B. Further mutual occlusion experiments demonstrated that PKC and CaMKII share a common signaling pathway in the potentiation of NMDAR trafficking and long-term potentiation (LTP) induction. Our results revealed that PKC promotes NMDA receptor trafficking and induces synaptic plasticity through indirectly triggering CaMKII autophosphorylation and subsequent increased association with NMDARs.
- Published
- 2011