CaMKII/NMDA 受体复合物通过激酶依赖和非依赖机制控制海马突触传递。

The CaMKII/NMDA receptor complex controls hippocampal synaptic transmission by kinase-dependent and independent mechanisms.

机构信息

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, 94158, USA.

Department of Psychiatry, University of California, San Francisco, San Francisco, CA, 94158, USA.

出版信息

Nat Commun. 2018 May 25;9(1):2069. doi: 10.1038/s41467-018-04439-7.

CaMKII is one of the most studied synaptic proteins, but many critical issues regarding its role in synaptic function remain unresolved. Using a CRISPR-based system to delete CaMKII and replace it with mutated forms in single neurons, we have rigorously addressed its various synaptic roles. In brief, basal AMPAR and NMDAR synaptic transmission both require CaMKIIα, but not CaMKIIβ, indicating that, even in the adult, synaptic transmission is determined by the ongoing action of CaMKIIα. While AMPAR transmission requires kinase activity, NMDAR transmission does not, implying a scaffolding role for the CaMKII protein instead. LTP is abolished in the absence of CaMKIIα and/or CaMKIIβ and with an autophosphorylation impaired CaMKIIα (T286A). With the exception of NMDAR synaptic currents, all aspects of CaMKIIα signaling examined require binding to the NMDAR, emphasizing the essential role of this receptor as a master synaptic signaling hub.

钙调蛋白依赖性蛋白激酶 II（CaMKII）是研究最为广泛的突触蛋白之一，但关于其在突触功能中的作用仍有许多关键问题尚未解决。我们使用基于 CRISPR 的系统在单个神经元中删除 CaMKII 并替换为突变形式，从而严格解决了其各种突触作用。简而言之，基础 AMPAR 和 NMDAR 突触传递都需要 CaMKIIα，但不需要 CaMKIIβ，这表明即使在成年期，突触传递也由 CaMKIIα 的持续作用决定。虽然 AMPAR 传递需要激酶活性，但 NMDAR 传递不需要，这意味着 CaMKII 蛋白具有支架作用。在缺乏 CaMKIIα 和/或 CaMKIIβ 的情况下，长时程增强（LTP）被消除，并且 CaMKIIα（T286A）的自身磷酸化受损。除了 NMDAR 突触电流外，所检查的 CaMKIIα 信号的所有方面都需要与 NMDAR 结合，这强调了该受体作为主突触信号枢纽的重要作用。