Document Type
Article
Publication Date
1-29-2020
Abstract
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.
Recommended Citation
Washburn, Halley R.; Xia, Nan L.; Zhou, Wei; Mao, Yu-Ting; and Dalva, Matthew B., "Positive surface charge of GluN1 N-terminus mediates the direct interaction with EphB2 and NMDAR mobility." (2020). Department of Neuroscience Faculty Papers. Paper 45.
https://jdc.jefferson.edu/department_neuroscience/45
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Language
English
Comments
This article is the author’s final published version in Nature Communications, Volume 11, Issue 1, January 2020, Article number 570.
The published version is available at https://doi.org/10.1038/s41467-020-14345-6. Copyright © Washburn et al.