Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, 199 Renai Road, Suzhou, 215123, Jiangsu, China.
Department of Anatomy and Neurobiology, Zhongshan School of Medicine, SunYat-sen University, Guangzhou, 510080, China.
Biochem Biophys Res Commun. 2021 Jan 1;534:323-329. doi: 10.1016/j.bbrc.2020.11.085. Epub 2020 Nov 25.
The binding of calmodulin (CaM) to NMDAR (N-methyl-D-aspartate receptor) GluN1 C-terminus is required for cacium (Ca)/calmodulin (CaM)-dependent inactivation of NMDAR. Previously, we found that GluN1 C-terminus translocated to nucleus, and regulated synaptic transmission. However, whether GluN1 C-terminus containing the nuclear localization signaling regulates the cellular distribution of CaM, and the CaM binding are not clear. In this study, we found that the 10 positive residues of GluN1 C-terminus determined the translocation of CaM to the nucleus. RNA sequencing data showed that CaM could regulate the genes expression of multiple cell surface membrane receptors. This was confirmed by electrophysiology data that the 10A mutation of GluN1 C-terminus increased the NMDAR/AMAPR-mediated synaptic transduction.
钙调蛋白（CaM）与 N-甲基-D-天冬氨酸受体（NMDAR）GluN1 C 端的结合对于钙离子（Ca）/钙调蛋白（CaM）依赖性 NMDAR 失活是必需的。先前，我们发现 GluN1 C 端易位到细胞核，并调节突触传递。然而，GluN1 C 端是否含有核定位信号调节 CaM 的细胞分布以及 CaM 的结合尚不清楚。在这项研究中，我们发现 GluN1 C 端的 10 个正电荷残基决定了 CaM 向核内的易位。RNA 测序数据表明，CaM 可以调节多个细胞表面膜受体的基因表达。这一结论得到了电生理学数据的证实，即 GluN1 C 端的 10A 突变增加了 NMDAR/AMAPR 介导的突触转导。
