{
  "abstract": "Precise control of synapse formation is essential for brain function. Adhesion-GPCRs combine adhesion, signaling, and scaffold recruitment to regulate synapse formation, yet their mechanisms of action remain unclear. Here, we identify nanoscale clustering of the adhesion-GPCR Latrophilin-3 as a key mechanism regulating excitatory synapse assembly. We find that endogenous Latrophilin-3 forms densely packed nanoclusters, with larger nanoclusters enriched at excitatory synapses. To probe the functional significance of Latrophilin-3 clustering, we engineered an optogenetically controlled Latrophilin-3. Light-induced Latrophilin-3 clustering triggered robust excitatory synapse formation, which required both Latrophilin-3-mediated G-protein signaling and postsynaptic scaffold recruitment. Strikingly, clustering of a mutant Latrophilin-3 lacking known ligand-binding domains still promoted synapse formation, indicating that Latrophilin-3 ligands induce synapse assembly primarily by clustering Latrophilin-3. Our findings suggest a general paradigm by which extracellular ligand-induced clustering activates adhesion-GPCRs by generating compartmentalized signaling, which in the case of Latrophilin-3, cooperates with postsynaptic scaffold recruitment to drive synapse assembly.",
  "abstract_shown": true,
  "affiliations": [
    "Stanford University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "C. Huyan"
    },
    {
      "name": "A. Bhat"
    },
    {
      "name": "G. Landa"
    },
    {
      "name": "T. C. Sudhof"
    },
    {
      "affs": [
        0
      ],
      "name": "A. R. Dunn"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fjnh5r11nh1ft.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.12.757884",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.12.757884v1.full",
  "id": "fjnh5r11nh1ft",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.12.757884v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2804|Neuroscience and Neuropharmacology Research"
    ]
  ],
  "openalex": "W7221826546",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.12.757884v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-12",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fjnh5r11nh1ft.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:41Z",
      "native_id": "10.64898/2026.10.12.757884",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.12.757884v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Clustering of the Adhesion-GPCR Latrophilin-3 Drives Excitatory Synapse Assembly",
  "title_text": "Clustering of the Adhesion-GPCR Latrophilin-3 Drives Excitatory Synapse Assembly",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:41Z",
  "url": "https://research.draconitic.com/paper/fjnh5r11nh1ft",
  "venue": "bioRxiv",
  "versions": []
}