{
  "abstract": "Synaptic transmission requires precise nanoscale alignment of presynaptic release machinery and postsynaptic receptor nanodomains. However, the molecular links bridging these subsynaptic elements remain unresolved. We identify mammalian neurexin-1γ as a presynaptic organizer that directly couples release sites to AMPAR nanodomains. Using complementary mouse lines, an epitope-tagged Nrxn1γ knockin and an Nrxn1γ knockout, and a multimodal approach, we find that neurexin-1γ is enriched at presynaptic release sites precisely opposite AMPAR nanoclusters. Nrxn1γ deletion perturbs synaptic nanoarchitecture, impairs vesicle docking and release, and disrupts transsynaptic nanocolumn alignment and AMPAR positioning, leading to broad deficits in both basal and evoked synaptic transmission, plasticity, and cognitive function. Mechanistically, neurexin-1γ directly binds AMPAR N-termini via its extracellular heparan sulfate glycans, anchoring them with nanoscale precision to neurotransmitter release sites. Our findings establish neurexin-1γ as a nanoscale transsynaptic bridge for optimal synaptic function and circuit activity, revealing an unconventional role for this minimal neurexin variant.",
  "abstract_shown": true,
  "affiliations": [
    "PrairieNeuro Research Centre, Kleysen Institute for Advanced Medicine, Health Sciences Centre, Winnipeg, MB, R3E 0Z3, Canada",
    "Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, R3E 0J9, Canada",
    "These authors contributed equally to this work",
    "Program in Biomedical Engineering, University of Manitoba",
    "Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, West Virginia, USA",
    "Department of Cell Biology and Anatomy, Alberta Children’s Hospital Research Institute, University of Calgary",
    "Hotchkiss Brain Institute, University of Calgary",
    "Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg, MB, R3E 3P4, Canada",
    "Department of Internal Medicine, University of Manitoba, Winnipeg, MB, R3A 1R9, Canada.",
    "Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, R3E 0J9, Canada.",
    "Department of Cell Biology, College of Medicine, University of Oklahoma Health Campus, Oklahoma City, Oklahoma, USA",
    "The Children’s Hospital Research Institute of Manitoba, Winnipeg, MB, R3E 3P4, Canada",
    "Lead contact"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 18,
  "authors": [
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        0,
        1
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      "name": "Nirmala Padmanabhan"
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        1
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      "name": "Rebecca E. Twilley"
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      "name": "Shinichiro Oku"
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      "name": "Mir Sohayeb Rabbi"
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      "name": "Adam Skeens"
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        4
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      "name": "Grace Jones"
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        6
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      "name": "Sandesh Acharya"
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      "name": "Mohammed Abrar Basha"
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      "name": "Dinu Rajapakse"
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    {
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      "name": "Cosette Koltek"
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      "name": "Nabiha Ameena"
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      "name": "Noushin Ahmadpour"
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        7
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      "name": "Ying Lao"
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      "name": "Jiami Guo"
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      "name": "Rene P. Zahedi"
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      "name": "Mohiuddin Ahmad"
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      "name": "Martin Hruska"
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    {
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        3,
        11,
        12
      ],
      "name": "Tabrez J. Siddiqui"
    }
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  "bibtex": "https://research.draconitic.com/paper/ed18fffjv2tp4.bib",
  "cited_by": 1,
  "doi": "10.1016/j.neuron.2026.06.018",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13584197/",
  "id": "ed18fffjv2tp4",
  "issns": [
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    "1097-4199"
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  "language": "en",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
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  "pmcid": "PMC13584197",
  "pmid": "42480538",
  "published": "2026-07-21",
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  "ris": "https://research.draconitic.com/paper/ed18fffjv2tp4.ris",
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Neuroscience and Neuropharmacology Research",
      "subfield": "neuroscience"
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  "title": "Neurexin-1γ drives synaptic transmission through structural integration of neurotransmitter release machinery and postsynaptic receptor nanodomains",
  "title_text": "Neurexin-1γ drives synaptic transmission through structural integration of neurotransmitter release machinery and postsynaptic receptor nanodomains",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:20:33Z",
  "url": "https://research.draconitic.com/paper/ed18fffjv2tp4",
  "venue": "Neuron",
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}