CaMKII autophosphorylation is the only enzymatic event required for synaptic memory

• 成果类型: Article
• 署名作者: Chen, Xiumin; Cai, Qixu; Zhou, Jing; Pleasure, Samuel J.; Schulman, Howard; Zhang, Mingjie; Nicoll, Roger A.
• 署名单位: Soochow University - China; Soochow University - China; University of California System; University of California San Francisco; Hong Kong University of Science & Technology; Xiamen University; University of California System; University of California San Francisco; Stanford University; Southern University of Science & Technology
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11609
• DOI: 10.1073/pnas.2402783121
• 发表日期: 2024-06-25
• 关键词: long-term potentiation; protein-kinase-ii; postsynaptic density; nmda receptors; ltp; maintenance; plasticity; subunit; binding; transmission

摘要

Ca 2+ /calmodulin (CaM) - dependent kinase II (CaMKII) plays a critical role in long - term potentiation (LTP), a well - established model for learning and memory through the enhancement of synaptic transmission. Biochemical studies indicate that CaMKII catalyzes a phosphotransferase (kinase) reaction of both itself (autophosphorylation) and of multiple downstream target proteins. However, whether either type of phosphorylation plays any role in the synaptic enhancing action of CaMKII remains hotly contested. We have designed a series of experiments to define the minimal requirements for the synaptic enhancement by CaMKII. We find that autophosphorylation of T286 and further binding of CaMKII to the GluN2B subunit are required both for initiating LTP and for its maintenance (synaptic memory). Once bound to the NMDA receptor, the synaptic action of CaMKII occurs in the absence of target protein phosphorylation. Thus, autophosphorylation and binding to the GluN2B subunit are the only two requirements for CaMKII in synaptic memory.