ArticleScientific reports2023
The intracellular domain of major histocompatibility class-I proteins is essential for maintaining excitatory spine density and synaptic ultrastructure in the brain.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- Immune-mediated excitotoxicity in brain disorders.Nature reviews. Immunology · 2026Review
- The neuroimmune system and cognition.Nature immunology · 2026Review
- Immune cells promote paralytic disease in mice infected with enterovirus D68.The Journal of clinical investigation · 2025Article
- Neurological Complications in Inborn Errors of Immunity: A Scoping Review of Clinical Spectrum, Pathophysiological Mechanisms, and Therapeutic Strategies.Clinical reviews in allergy & immunology · 2025Article
- Structural plasticity of pyramidal cell neurons measured after FLASH and conventional dose-rate irradiation.Brain structure & function · 2025Article
- Toward curing neurological autoimmune disorders: Biomarkers, immunological mechanisms, and therapeutic targets.Neuron · 2025Review
- Review
- Structural plasticity of pyramidal cell neurons measured after FLASH and conventional dose-rate irradiation.Research square · 2024Article
- Outside-in signaling through the major histocompatibility complex class-I cytoplasmic tail modulates glutamate receptor expression in neurons.Scientific reports · 2023Article
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Major histocompatibility complex class I (MHC-I) proteins are expressed in neurons, where they regulate synaptic plasticity. However, the mechanisms by which MHC-I functions in the CNS remains unknown. Here we describe the first structural analysis of a MHC-I protein, to resolve underlying mechanisms that explains its function in the brain. We demonstrate that Y321F mutation of the conserved cytoplasmic tyrosine-based endocytosis motif YXXΦ in MHC-I affects spine density and synaptic structure without affecting neuronal complexity in the hippocampus, a region of the brain intimately involved in learning and memory. Furthermore, the impact of the Y321F substitution phenocopies MHC-I knock-out (null) animals, demonstrating that reverse, outside-in signalling events sensing the external environment is the major mechanism that conveys this information to the neuron and this has a previously undescribed yet essential role in the regulation of synaptic plasticity.
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Registered trials
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