A5023213448- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Nicotinic Acetylcholine Receptors Study
- Marine Sponges and Natural Products
- Cellular transport and secretion
- Photoreceptor and optogenetics research
- Marine Toxins and Detection Methods
- Epilepsy research and treatment
- Chemical Synthesis and Analysis
- Neuroinflammation and Neurodegeneration Mechanisms
- Lipid Membrane Structure and Behavior
- Neurobiology and Insect Physiology Research
- Memory and Neural Mechanisms
- Molecular Sensors and Ion Detection
- Synthetic Organic Chemistry Methods
- RNA regulation and disease
- RNA and protein synthesis mechanisms
- Neural dynamics and brain function
- Mitochondrial Function and Pathology
- Genetics and Neurodevelopmental Disorders
- Chemical synthesis and alkaloids
- Galectins and Cancer Biology
- Photochromic and Fluorescence Chemistry
- Glycosylation and Glycoproteins Research
Northwestern University
2015-2025
Northwestern University
2023
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2021
MRC Laboratory of Molecular Biology
2021
Vanderbilt University
2021
National University of Singapore
2021
Stony Brook University
2021
Emory University
2021
The University of Texas Health Science Center at Houston
2021
Columbia University
2021
Non-NMDA glutamate receptor subunits of the AMPA-preferring subfamily combine to form ion channels with heterogeneous functional properties. We have investigated effects RNA editing at Q/R site, splice variation “flip/flop” cassette, and multimeric subunit assembly on single-channel conductance kinetic properties recombinant AMPA receptors formed from GluR2 GluR4 expressed in HEK 293 cells. found that was dependent site state comprising channel. Calcium-permeable (unedited) had resolvable...
Formation of mature excitatory synapses requires the assembly and delivery NMDA receptors to neuronal plasma membrane. A key step in trafficking is exit newly assembled from endoplasmic reticulum (ER). Here we report identification an RXR-type ER retention/retrieval motif C-terminal tail receptor subunit NR1 that regulates surface expression heterologous cells neurons. In addition, show PKC phosphorylation alternatively spliced consensus type I PDZ-binding domain suppress retention. These...
1. Whole‐cell recordings were made from cerebellar granule cells cultured in high‐K+ medium to induce expression of Ca(2+)‐permeable AMPA receptors. Current‐voltage (I‐V) plots agonist‐evoked responses showed varying degrees inward rectification, but became linear within 5‐10 min. 2. Recombinant kainate receptors, composed GluR6(Q)/KA‐2 subunits, exhibited rectifying whole‐cell I‐V that outside‐out patches. 3. Loss rectification was prevented by including 100 microM spermine the pipette;...
The site of induction long-term potentiation (LTP) at mossy fiber–CA3 synapses in the hippocampus is unresolved, with data supporting both pre- and postsynaptic mechanisms. Here we report that fiber LTP was reduced by perfusion neurons peptides antibodies interfere binding EphB receptor tyrosine kinases (EphRs) to PDZ protein GRIP. Mossy also extracellular application soluble forms B-ephrins, which are normally membrane-anchored presynaptic ligands for receptors. ephrins increased basal...
1. Patch-clamp methods have been used to examine single-channel properties of recombinant GluR5 and GluR6 kainate-preferring glutamate receptors which differ in a single amino acid residue as result RNA editing at the Q/R (glutamine/arginine) site. Subunits were expressed alone or combination with high-affinity kainate receptor subunit KA - 2 transfected human embryonic kidney (HEK-293) cells. 2. In outside-out patches, unedited homomeric GluR6(Q) exhibited directly resolved...
Cortical information storage requires combined changes in connectivity and synaptic strength between neurons, but the signaling mechanisms underlying this two-step wiring plasticity are unknown. Because acute 17beta-estradiol (E2) modulates cortical memory, we examined its effects on spine morphogenesis, AMPA receptor trafficking, GTPase neurons. Acute E2 application resulted a rapid, transient increase density, accompanied by temporary formation of silent synapses through reduced surface...
The pathophysiology of drug-resistant pediatric epilepsy is unknown. Flow cytometric analysis inflammatory leukocytes in resected brain tissues from 29 patients with genetic (focal cortical dysplasia) or acquired (encephalomalacia) demonstrated significant infiltration blood-borne myeloid cells and memory CD4+ CD8+ T cells. Significantly, proinflammatory (IL-17– GM-CSF–producing) γδ were concentrated epileptogenic lesions, their numbers positively correlated disease severity. Conversely,...
Seizures are a frequent complication of adult-type diffuse gliomas, and often difficult to control with medications. Gliomas mutations in isocitrate dehydrogenase 1 or 2 (IDHmut) more likely than IDH–wild type (IDHwt) gliomas cause seizures as part their initial clinical presentation. However, whether IDHmut is also associated during the remaining disease course, inhibitors can reduce seizure risk, unclear. Clinical multivariable analyses showed that preoperative seizures, glioma location,...
To understand the physiological role of kainate receptors and their participation in seizure induction animal models epilepsy, it will be necessary to develop a comprehensive description action CA3 region hippocampus. Activation presynaptic depresses excitatory synaptic transmission at mossy fiber associational-commissural inputs pyramidal neurons (Vignes et al., 1998; Bortolotto 1999; Kamiya Ozawa, 2000). In this study, we use gene-targeted mice lacking glutamate receptor 5 (GluR5) or GluR6...
Multimeric assemblies of kainate (KA) receptor subunits form glutamate-gated ion channels that mediate EPSCs and function as presynaptic modulators neurotransmitter release at some central synapses. The KA2 subunit is a likely constituent many neuronal receptors, because it widely expressed in most neurons the CNS. We have studied effect genetic ablation this on synaptic transmission mossy-fiber–CA3 pyramidal cell synapse hippocampal slices, where receptors are localized to both postsynaptic...
Kainate receptors function as mediators of postsynaptic currents and presynaptic modulators synaptic transmission at mossy fiber synapses. Despite intense research into the physiological properties kainate receptors, their subunit composition in compartments is unclear. Here we describe distribution receptor subunits synapses using subunit-selective antibodies knock-out mice. We provide morphological evidence for localization KA1 KA2 Immunogold staining was commonly seen contacts vesicular...
Auxiliary proteins modify the biophysical function and pharmacological properties of ionotropic glutamate receptors likely are important components receptor signaling complexes in vivo. The neuropilin tolloid-like (NETO) 1 NETO2, two closely related CUB domain-containing integral membrane proteins, were identified recently as auxiliary that slowed GluK2a kainate current kinetics without impacting localization. Here we demonstrate NETO2 profoundly slows desensitization rate GluK1 receptors,...
Abstract Activation of NMDA receptors (NMDAR) in the hippocampus is essential for formation contextual and trace memory. However, role individual NMDAR subunits molecular mechanisms contributing to these memory processes not known. Here we demonstrate, using intrahippocampal injection subunit‐selective compounds, that NR2A‐preferring antagonist impaired fear conditioning as well learning‐induced increase nuclear protein c‐Fos. The NR2B‐specific antagonist, on other hand, selectively blocked...
The kainate receptor subunit KA2 does not form functional homomeric channels despite its structural similarity to the glutamate 5-7subunits and high agonist binding affinity in vitro assays. In this study, we first demonstrate that receptors fail reach plasma membrane then identify molecular mechanisms preventing surface expression. Specifically, show subunits homooligomeric are confined endoplasmic reticulum (ER). We that, both heterologous expression systems primary neurons, intracellular...
Activity-driven changes in the neuronal surface glycoproteome are known to occur with synapse formation, plasticity, and related diseases, but their mechanistic basis significance unclear. Here, we observed that N -glycans on glycoproteins of dendrites shift from immature mature forms containing sialic acid response increased activation. In exploring these -glycosylation alterations, discovered they result growth proliferation Golgi satellites scattered throughout dendrite. formed during...