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Positive surface charge of GluN1 N-terminus mediates the direct interaction with EphB2 and NMDAR mobility
- Source :
- Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020), Nature Communications
- Publication Year :
- 2020
- Publisher :
- Nature Publishing Group, 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.<br />NMDA receptors undergo constant cycling into and out of the postsynaptic density. Here authors show that NMDAR's GluN1 subunit is required to maintain NMDARs at dendritic spine synapses by direct extracellular interaction with the receptor tyrosine kinase EphB2.
- Subjects :
- 0301 basic medicine
Models, Molecular
Dendritic spine
Glycosylation
Protein Conformation
General Physics and Astronomy
Ion channels in the nervous system
Nervous System
Receptor tyrosine kinase
Ion Channels
Mice
0302 clinical medicine
lcsh:Science
Neurons
Multidisciplinary
biology
Chemistry
musculoskeletal, neural, and ocular physiology
Glutamate receptor
NMDA receptor
biological phenomena, cell phenomena, and immunity
Intracellular
psychological phenomena and processes
Receptor, EphB2
Science
Dendritic Spines
Biophysics
Molecular neuroscience
Receptors, N-Methyl-D-Aspartate
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
mental disorders
Extracellular
Animals
Humans
Protein Interaction Domains and Motifs
Ion channel
Neurosciences
General Chemistry
Synaptic development
030104 developmental biology
HEK293 Cells
nervous system
Synapses
biology.protein
Tyrosine
lcsh:Q
Postsynaptic density
030217 neurology & neurosurgery
Neuroscience
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....02e9684f8ccdcc86b8f4f4fd1fe9329f