{
  "abstract": "Synapses, prototypic sites for neuronal communication, are key to brain function. Their organization and properties are instructed by synaptic cell adhesion molecules (sCAMs) that may operate independently or in coordination through yet unknown linker proteins. Here, we used multi-epitope affinity-purifications combined with quantitative mass spectrometry and immuno-EM to comprehensively map synaptic protein networks in the mouse brain. We identify a pre-synaptic core-module assembled from the major sCAMs, Neurexins1-3 and LAR-type receptor protein-tyrosine-phosphatases (PTPRs), and the previously uncharacterized tetraspanins T178A/B. These ternary Neurexin-T178-PTPR complexes form through their trans-membrane domains and assemble during biogenesis in the ER. Loss of T178B leads to module destabilization, accompanied by strong reduction of LAR-PTPRs and re-distribution of synaptic Neurexins. At synapses, the Neurexin-T178-PTPR module recruits stable trans-synaptic protein networks thereby interlinking machineries of the pre-synaptic active zone and establishing stable associations with post-synaptic neurotransmitter receptors. This work uncovers a widely distributed core-module for synaptic adhesion and trans-synaptic signaling in the mammalian brain.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Physiology, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 7, Freiburg, Germany",
    "Institute of Physiology, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 7, Freiburg, Germany. jochen.schwenk@physiologie.uni-freiburg.de",
    "Department of Neurophysiology, Keio University School of Medicine, Tokyo, Japan",
    "Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden",
    "Department of Laboratory Medicine, Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden",
    "Biozentrum of the University of Basel, Basel, Switzerland",
    "Logopharm GmbH, Schlossstr. 14, March-Buchheim, Germany",
    "Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden",
    "Center for Basics in NeuroModulation, Breisacherstr. 4, Freiburg, Germany. bernd.fakler@physiologie.uni-freiburg.de",
    "Institute of Physiology, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 7, Freiburg, Germany. bernd.fakler@physiologie.uni-freiburg.de",
    "Signalling Research Centres BIOSS and CIBSS, Schänzlestr. 18, Freiburg, Germany. bernd.fakler@physiologie.uni-freiburg.de"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Spyros Thivaios",
      "orcid": "0000-0001-9519-4538"
    },
    {
      "affs": [
        1
      ],
      "name": "Jochen Schwenk",
      "orcid": "0000-0003-3664-9795"
    },
    {
      "affs": [
        0
      ],
      "name": "Aline Bréchet"
    },
    {
      "affs": [
        0
      ],
      "name": "Sami Boudkkazi"
    },
    {
      "affs": [
        0
      ],
      "name": "Nithya Sethumadhavan",
      "orcid": "0000-0003-4233-6074"
    },
    {
      "affs": [
        0
      ],
      "name": "Phil Henneken"
    },
    {
      "affs": [
        2
      ],
      "name": "Eriko Miura",
      "orcid": "0000-0002-5237-9580"
    },
    {
      "affs": [
        2
      ],
      "name": "Ayumi Hayashi"
    },
    {
      "affs": [
        0
      ],
      "name": "Maciej K. Kocylowski",
      "orcid": "0000-0001-8645-6727"
    },
    {
      "affs": [
        0
      ],
      "name": "Alexander Haupt",
      "orcid": "0000-0001-5647-5724"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Debora Kaminski"
    },
    {
      "affs": [
        5
      ],
      "name": "Dietmar Schreiner"
    },
    {
      "affs": [
        5
      ],
      "name": "Agata Nowacka",
      "orcid": "0000-0001-9289-5785"
    },
    {
      "affs": [
        0
      ],
      "name": "Jean-Baptiste van den Broucke",
      "orcid": "0009-0006-9113-905X"
    },
    {
      "affs": [
        0
      ],
      "name": "Ákos Kulik",
      "orcid": "0000-0001-8712-4636"
    },
    {
      "affs": [
        0,
        6
      ],
      "name": "Uwe Schulte",
      "orcid": "0000-0003-3557-0591"
    },
    {
      "affs": [
        3,
        4,
        7
      ],
      "name": "Fredrik H. Sterky",
      "orcid": "0000-0001-8881-0523"
    },
    {
      "affs": [
        2
      ],
      "name": "Michisuke Yuzaki",
      "orcid": "0000-0002-5750-3544"
    },
    {
      "affs": [
        5
      ],
      "name": "Peter Scheiffele",
      "orcid": "0000-0002-9516-9399"
    },
    {
      "affs": [
        8,
        9,
        10
      ],
      "name": "Bernd Fakler",
      "orcid": "0000-0001-7264-6423"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9adwy57cj93k9.bib",
  "cited_by": 6,
  "doi": "10.1038/s41467-026-77377-4",
  "fulltext_url": null,
  "id": "9adwy57cj93k9",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-77377-4",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2804|Neuroscience and Neuropharmacology Research"
    ]
  ],
  "openalex": "W4400830032",
  "pdf_url": null,
  "pmcid": "PMC13546301",
  "pmid": "42701130",
  "published": "2026-09-05",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/9adwy57cj93k9.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T13:21:11Z",
      "native_id": "W4400830032",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41467-026-77377-4"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Neuroscience and Neuropharmacology Research",
      "subfield": "neuroscience"
    }
  ],
  "title": "Ternary Neurexin-T178-PTPR complexes represent a pre-synaptic core-module of neuronal synapse organization",
  "title_text": "Ternary Neurexin-T178-PTPR complexes represent a pre-synaptic core-module of neuronal synapse organization",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:14Z",
  "url": "https://research.draconitic.com/paper/9adwy57cj93k9",
  "venue": "Nature Communications",
  "versions": []
}