Agonist binding to the NMDA receptor drives movement of its cytoplasmic domain without ion flow
The NMDA receptor (R) plays important roles in brain physiology and pathology as an ion channel. Here we examine the ion flow-independent coupling of agonist to the NMDAR cytoplasmic domain (cd). We measure FRET between fluorescently tagged cytoplasmic domains of GluN1 subunits of NMDARs expressed i...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2015-11, Vol.112 (47), p.14705-14710 |
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| container_issue | 47 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Dore, Kim Aow, Jonathan Malinow, Roberto |
| description | The NMDA receptor (R) plays important roles in brain physiology and pathology as an ion channel. Here we examine the ion flow-independent coupling of agonist to the NMDAR cytoplasmic domain (cd). We measure FRET between fluorescently tagged cytoplasmic domains of GluN1 subunits of NMDARs expressed in neurons. Different neuronal compartments display varying levels of FRET, consistent with different NMDARcd conformations. Agonist binding drives a rapid and transient ion flow-independent reduction in FRET between GluN1 subunits within individual NMDARs. Intracellular infusion of an antibody targeting the GluN1 cytoplasmic domain blocks agonistdriven FRET changes in the absence of ion flow, supporting agonistdriven movement of the NMDARcd. These studies indicate that extracellular ligand binding to the NMDAR can transmit conformational information into the cell in the absence of ion flow. |
| doi_str_mv | 10.1073/pnas.1520023112 |
| format | Article |
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| source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Binding sites Biological Sciences Brain Cytoplasm Cytoplasm - metabolism Fluorescence Resonance Energy Transfer Green Fluorescent Proteins - metabolism Ion Transport Ligands Neurons Protein Structure, Tertiary Protein Subunits - metabolism Receptors, N-Methyl-D-Aspartate - agonists Receptors, N-Methyl-D-Aspartate - chemistry Time Factors |
| title | Agonist binding to the NMDA receptor drives movement of its cytoplasmic domain without ion flow |
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