Disrupted surface cross-talk between NMDA and Ephrin-B2 receptors in anti-NMDA encephalitis
Abstract
Autoimmune synaptic encephalitides are recently described human brain diseases leading to psychiatric and neurological syndromes through inappropriate brain-autoantibody interactions. The most frequent synaptic autoimmune encephalitis is associated with autoantibodies against extracellular domains of the glutamatergic N-methyl-d-aspartate receptor, with patients developing psychotic and neurological symptoms in an autoantibody titre-dependent manner. Although N-methyl-d-aspartate receptors are the primary target of these antibodies, the cellular and molecular pathway(s) that rapidly lead to N-methyl-d-aspartate receptor dysfunction remain poorly understood. In this report, we used a unique combination of high-resolution nanoparticle and bulk live imaging approaches to demonstrate that anti-N-methyl-d-aspartate receptor autoantibodies from patients with encephalitis strongly alter, in a time-dependent manner, the surface content and trafficking of GluN2-NMDA receptor subtypes. Autoantibodies laterally displaced surface GluN2A-NMDA receptors out of synapses and completely blocked synaptic plasticity. This loss of extrasynaptic and synaptic N-methyl-d-aspartate receptor is prevented both in vitro and in vivo, by the activation of EPHB2 receptors. Indeed, the anti-N-methyl-d-aspartate receptor autoantibodies weaken the interaction between the extracellular domains of the N-methyl-d-aspartate and Ephrin-B2 receptors. Together, we demonstrate that the anti-N-methyl-d-aspartate rece…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Experiments where patients' antibodies were added to cultures of hippocampal neurons or infused into the hippocampus of rodents showed specific antibody-mediated internalization of NMDAR and alteration of the mechanisms of synaptic plasticity.
“Experiments where patients’ antibodies were added to cultures of hippocampal neurons or infused into the hippocampus of rodents showed specific antibody-mediated internalization of NMDAR and alteration of the mechanisms of synaptic plasticity.9, 10”
From Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study (2013) · cites this paper as [10]
Cites
Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies
Dalmau, J., Gleichman, A. J., Hughes, E. G., Rossi, J. E., Peng, X., Lai, M., Dessain, S. K., Rosenfeld, M. R., Balice-Gordon, R., & Lynch, D. R. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70224-2 · Cited by 3,488 · see citing works
Dalmau, J., Tüzün, E., Wu, H., Masjuan, J., Rossi, J. E., Voloschin, A., Baehring, J. M., Shimazaki, H., Koide, R., King, D., et al. (2007) · Annals of Neurology · doi:10.1002/ana.21050 · Cited by 2,492 · see citing works
NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders
Lau, C. G., & Zukin, R. S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2153 · Cited by 1,159 · cited 1× · see citing works
“In the basal conditions, GluN2A-NMDA receptors directly interact with intracellular PDZ domain-containing scaffold proteins (Lau and Zukin, 2007) and transmembrane EPHB2Rs (Dalva et al., 2000), leading to a high synaptic retention of NMDA receptors.”
BackgroundRecycling Endosomes Supply AMPA Receptors for LTP
Park, M., Penick, E. C., Edwards, J. G., Kauer, J. A., & Ehlers, M. D. (2004) · Science · doi:10.1126/science.1102026 · Cited by 730 · see citing works
Lu, J., Helton, T. D., Blanpied, T. A., Rácz, B., Newpher, T. M., Weinberg, R. J., & Ehlers, M. D. (2007) · Neuron · doi:10.1016/j.neuron.2007.06.041 · Cited by 273 · see citing works
Groc, L., Choquet, D., Stephenson, F. A., Verrier, D., Manzoni, O. J., & Chavis, P. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.1772-07.2007 · Cited by 225 · see citing works
Self-citationNeurotoxic autoantibodies mediate congenital cortical impairment of offspring in maternal lupus
Lee, J. Y., Huerta, P. T., Zhang, J., Kowal, C., Bertini, E., Volpe, B. T., & Diamond, B. (2009) · Nature Medicine · doi:10.1038/nm.1892 · Cited by 163 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Titulaer, M. J., McCracken, L., Gabilondo, I., Armangué, T., Glaser, C., Iizuka, T., Honig, L. S., Benseler, S. M., Kawachi, I., Martinez-Hernandez, E., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70310-1 · Cited by 3,165 · see citing works
NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease
Paoletti, P., Bellone, C., & Zhou, Q. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3504 · Cited by 2,523 · see citing works
Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels
Hansen, K. B., Wollmuth, L. P., Bowie, D., Furukawa, H., Menniti, F. S., Sobolevsky, A. I., Swanson, G. T., Swanger, S. A., Greger, I. H., Nakagawa, T., et al. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000131 · Cited by 686 · see citing works
Surface diffusion of astrocytic glutamate transporters shapes synaptic transmission
Murphy-Royal, C., Dupuis, J. P., Varela, J. A., Panatier, A., Pinson, B., Baufreton, J., Groc, L., & Oliet, S. H. R. (2015) · Nature Neuroscience · doi:10.1038/nn.3901 · Cited by 252 · see citing works
Self-citationInfectious immunity in the central nervous system and brain function
Klein, R. S., Garber, C., & Howard, N. (2017) · Nature Immunology · doi:10.1038/ni.3656 · Cited by 235 · see citing works
Regulation of NMDA glutamate receptor functions by the GluN2 subunits
Vieira, M., Yong, X. L. H., Roche, K. W., & Anggono, V. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.14970 · Cited by 151 · see citing works
“, 2009), secreted proteases (Lesept, Chevilley, & Jezequel, 2016), growth factors (De Rossi, Harde, & Dupuis, 2016), cell surface receptors (Ladepeche et al., 2013; Mikasova et al., 2012) and hormones (Potier et al.”
Background
- Authors
- Mikasova, L., De Rossi, P., Bouchet, D., Georges, F., Rogemond, V., Didelot, A., Meissirel, C., Honnorat, J., & Groc, L.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Lyon 1 Université (FR)
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-04-27
- Volume
- 135
- Issue
- 5
- Pages
- 1606-1621
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2105127406
- Cited by
- 341
- References
- 7
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 30 · 2023: 28 · 2022: 19 · 2021: 25 · 2020: 32 · 2019: 21 · 2018: 26 · 2017: 28 · 2016: 31 · 2015: 27 · 2014: 26 · 2013: 19 · 2012: 2
- FWCI
- 15.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Autoimmune Neurological Disorders and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Keywords
- anti-NMDA receptor encephalitis, NMDA receptor antibodies, ephrin-B2, EphB2, synaptic plasticity, glutamatergic synapses
- MeSH terms
- Adult, Aged, Animals, Biophysics, Calcium, Cell Membrane, Cells, Cultured, Child, Child, Preschool, Electric Stimulation, Embryo, Mammalian, Encephalitis, Enzyme-Linked Immunosorbent Assay, Female, Hippocampus, Humans, Immunoglobulin G, Male, Middle Aged, Neurons, Tetrodotoxin, Tosyl Compounds, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation, Patch-Clamp Techniques, Excitatory Amino Acid Agents, Receptor Cross-Talk, Protein Subunits, Protein Transport, Sodium Channel Blockers, Receptors, Eph Family, Ephrins, Photobleaching, Immunoprecipitation, Mice, Rats, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
