Positive surface charge of GluN1 N-terminus mediates the direct interaction with EphB2 and NMDAR mobility.
Positive surface charge of GluN1 N-terminus mediates the direct interaction with EphB2 and NMDAR mobility.
复制标题
GluN1 N 端的正表面电荷介导与 EphB2 和 NMDAR 迁移率的直接相互作用。
DOI：
10.1038/s41467-020-14345-6
复制
发表时间：
2020
影响因子：
16.6
通讯作者：
Dalva,MatthewB
中科院分区：
文献类型：
--
作者：
Washburn,HalleyR;Xia,NanL;Zhou,Wei;Mao,Yu-Ting;Dalva,MatthewB
N-甲基-D-天冬氨酸型谷氨酸受体（NMDAR）在树突棘上的定位对于兴奋性突触传递和可塑性至关重要。NMDA受体不是停留在突触部位，而是经历不断的循环进出突触后密度。受体运动受到与NMDAR的胞内和胞外结构域两者的蛋白质-蛋白质相互作用的限制。细胞外相互作用对NMDAR迁移率的作用知之甚少。在这里，我们证明了NMDAR的GluN 1亚基中N-末端结构域的铰链区的正表面电荷是维持树突棘突触处的NMDAR所必需的，并且介导了与受体酪氨酸激酶EphB 2上带负电荷的磷酸酪氨酸的直接细胞外相互作用。通过突变GluN 1或敲低内源性EphB 2而丧失EphB-NMDAR相互作用增加NMDAR迁移率。这些发现开始定义一个机制，为细胞外相互作用介导的带电域。
Localization of the N-methyl-D-aspartate type glutamate receptor (NMDAR) to dendritic spines is essential for excitatory synaptic transmission and plasticity. Rather than remaining trapped at synaptic sites, NMDA receptors undergo constant cycling into and out of the postsynaptic density. Receptor movement is constrained by protein-protein interactions with both the intracellular and extracellular domains of the NMDAR. The role of extracellular interactions on the mobility of the NMDAR is poorly understood. Here we demonstrate that the positive surface charge of the hinge region of the N-terminal domain in the GluN1 subunit of the NMDAR is required to maintain NMDARs at dendritic spine synapses and mediates the direct extracellular interaction with a negatively charged phospho-tyrosine on the receptor tyrosine kinase EphB2. Loss of the EphB-NMDAR interaction by either mutating GluN1 or knocking down endogenous EphB2 increases NMDAR mobility. These findings begin to define a mechanism for extracellular interactions mediated by charged domains.