{
  "abstract": "GPR88 is an orphan GPCR with genetic variants associated with multiple neuropsychiatric conditions. GPR88 exhibits enriched expression in the striatum, olfactory tubercle, and inferior olive. Despite these functional associations, its endogenous ligand and its downstream molecular pathways remain unresolved. Here, we found that climbing fiber (CF)-localized GPR88 regulates CF-Purkinje cell synapses in the cerebellum and associative learning behaviors. The results support the CF-secreted protein C1ql1 as the ligand of GPR88 and further revealed that C1ql1 activates biased Gq signaling to enhance CF synapses. Last, we demonstrated that GPR88 anchors C1ql1 and, via C1ql1, forms a tripartite complex with the postsynaptic adhesion GPCR BAI3 in vitro. These findings resolve the orphan status of GPR88 and likely reveal a mechanism by which a secreted protein links two GPCRs to fine-tune synaptic signaling at pre- and postsynaptic sites.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen 518132, China.",
    "School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.",
    "NHC Key Laboratory of Otorhinolaryngology, Qilu Hospital and School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, China.",
    "Advanced Medical Research Institute, New Cornerstone Science Laboratory, Shandong University, Jinan, Shandong 250012, China.",
    "Shenzhen Key Laboratory of Biomolecular Assembling and Regulation, Shenzhen 518055, China.",
    "Department of Neuroscience and Brain Research Center, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.",
    "Department of Anatomy and K.K. Leung Brain Research Center, Fourth Military Medical University, Xi’an 710032, China.",
    "Institute of Brain Science and Brain-inspired Research, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, China.",
    "Institute for Biological Electron Microscopy, Southern University of Science and Technology, Shenzhen 518055, China.",
    "Shenzhen Medical Academy of Research and Translation, Shenzhen 518132, China."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Ying Han",
      "orcid": "0000-0002-4336-7967"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Qingbiao Meng",
      "orcid": "0009-0009-2901-1524"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Xuan Li",
      "orcid": "0009-0007-9266-497X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Qin Huang",
      "orcid": "0009-0007-4668-1576"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Liming Qin",
      "orcid": "0000-0003-1216-5278"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Liangyu Liao",
      "orcid": "0009-0006-3834-584X"
    },
    {
      "affs": [
        6
      ],
      "name": "Ke-Ke Xing",
      "orcid": "0000-0003-0617-0863"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Jie Cheng",
      "orcid": "0000-0001-9972-2166"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Lulu Guo",
      "orcid": "0000-0002-1309-6801"
    },
    {
      "affs": [
        7
      ],
      "name": "Chao Zhang",
      "orcid": "0000-0001-8760-0110"
    },
    {
      "affs": [
        6
      ],
      "name": "Tao Chen",
      "orcid": "0000-0003-1956-0553"
    },
    {
      "affs": [
        4,
        5,
        8
      ],
      "name": "Zhiyi Wei",
      "orcid": "0000-0002-4446-6502"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Xiao Yu",
      "orcid": "0000-0003-1119-8334"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Jin-Peng Sun",
      "orcid": "0000-0003-3572-1580"
    },
    {
      "affs": [
        0,
        1,
        9
      ],
      "name": "Bo Zhang",
      "orcid": "0000-0003-2451-0593"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/drmck7k63j5av.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aec0867",
  "fulltext_url": "https://europepmc.org/articles/PMC13715693",
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  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "heading",
      "Developmental Neuroscience"
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      "heading",
      "Neuroscience"
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      "heading",
      "Research Article"
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      "heading",
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    [
      "openalex",
      "2804|Neuroscience and Neuropharmacology Research"
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  "pdf_url": "https://europepmc.org/articles/PMC13715693?pdf=render",
  "pmcid": "PMC13715693",
  "pmid": "42950037",
  "published": "2026-10-28",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/drmck7k63j5av.ris",
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  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Neuroscience",
      "subfield": "neuroscience"
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  ],
  "title": "Trans-synaptic interaction of orphan GPCR GPR88 and adhesion GPCR BAI3 through C1ql1 maintains synapse integrity",
  "title_text": "Trans-synaptic interaction of orphan GPCR GPR88 and adhesion GPCR BAI3 through C1ql1 maintains synapse integrity",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:55Z",
  "url": "https://research.draconitic.com/paper/drmck7k63j5av",
  "venue": "Science Advances",
  "versions": []
}