title: Conformational signaling required for synaptic plasticity by the NMDA receptor complex.
abstract: The NMDA receptor (NMDAR) is known to transmit important information by conducting calcium ions. However, some recent studies suggest that activation of NMDARs can trigger synaptic plasticity in the absence of ion flow. Does ligand binding transmit information to signaling molecules that mediate synaptic plasticity? Using Förster resonance energy transfer (FRET) imaging of fluorescently tagged proteins expressed in neurons, conformational signaling is identified within the NMDAR complex that is essential for downstream actions. Ligand binding transiently reduces FRET between the NMDAR cytoplasmic domain (cd) and the associated protein phosphatase 1 (PP1), requiring NMDARcd movement, and persistently reduces FRET between the NMDARcd and calcium/calmodulin-dependent protein kinase II (CaMKII), a process requiring PP1 activity. These studies directly monitor agonist-driven conformational signaling at the NMDAR complex required for synaptic plasticity.
authors.affiliation: Center for Neural Circuits and Behavior, Department of Neuroscience and Section for Neurobiology, Division of Biology, University of California, San Diego, CA 92093.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Aow
authors.affiliation: Center for Neural Circuits and Behavior, Department of Neuroscience and Section for Neurobiology, Division of Biology, University of California, San Diego, CA 92093.
authors.forename: Kim
authors.initials: K
authors.lastname: Dore
authors.affiliation: Center for Neural Circuits and Behavior, Department of Neuroscience and Section for Neurobiology, Division of Biology, University of California, San Diego, CA 92093 rmalinow@ucsd.edu.
authors.forename: Roberto
authors.initials: R
authors.lastname: Malinow
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D008954:Models, Biological; D016202:N-Methylaspartate / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses
chemical_list: D000906:Antibodies; D016194:Receptors, N-Methyl-D-Aspartate; D049452:Green Fluorescent Proteins; D016202:N-Methylaspartate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D010749:Phosphoprotein Phosphatases
keywords: LTD; NMDAR-CaMKII interaction; NMDAR-PP1 FRET; ion-flow independent; long-term depression