ArticleNeuron2016
Structural Basis for Regulation of GPR56/ADGRG1 by Its Alternatively Spliced Extracellular Domains.
Article in Neuron, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 131 citations in OpenAlex.
- Review
- Ligand-tuned extracellular domain dynamics are correlated with signaling states in an adhesion GPCR.Science advances · 2026Article
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- Self-cleavage-dependent and -independent functions ofProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Structural basis of GAIN domain autoproteolysis and cleavage-resistance in the adhesion G-protein coupled receptors.Nature communications · 2026Article
- The Role of the TG2-GPR56 Complex in Cutaneous Squamous Cell Carcinoma (CSCC) Aggression and Therapeutic Resistance.International journal of molecular sciences · 2026Review
- The far extracellular CUB domain of the adhesion GPCR ADGRG6/GPR126 is a key regulator of receptor signaling.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Adhesion G-Protein Coupled Receptors in Neurological and Psychiatric Disorders.Journal of psychiatry and brain science · 2025Article
- Super-resolution mapping of the ankle link proteins ADGRV1 and PDZD7 in developing auditory hair cells.iScience · 2025Article
- Identification and localization of adhesion G protein-coupled receptor expression in the murine kidney.American journal of physiology. Renal physiology · 2025Article
- GPR56/ADGRG1 induces biased Rho-ROCK-MLC and JAK-STAT3 signaling to promote amoeboid-like morphology and IL-6 upregulation in melanoma cells.Cell communication and signaling : CCS · 2025Article
- Complex G-protein signaling of the adhesion GPCR, ADGRA3.The Journal of biological chemistry · 2025Article
- Mechanosensitive adhesion G protein-coupled receptors: Insights from health and disease.Genes & diseases · 2025Review
- Structural basis for regulation of CELSR1 by a compact module in its extracellular region.Nature communications · 2025Article
- Generic residue numbering of the GAIN domain of adhesion GPCRs.Nature communications · 2025Article
- Conformational coupling between extracellular and transmembrane domains modulates holo-adhesion GPCR function.Nature communications · 2024Article
- G protein selectivity profile of GPR56/ADGRG1 and its effect on downstream effectors.Research square · 2024Article
- G protein selectivity profile of GPR56/ADGRG1 and its effect on downstream effectors.Cellular and molecular life sciences : CMLS · 2024Article
- Mechanical force induced activation of adhesion G protein-coupled receptor.Mechanobiology in medicine · 2024Review
- Heterogeneity of tethered agonist signaling in adhesion G protein-coupled receptors.Cell chemical biology · 2024Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Adhesion G protein-coupled receptors (aGPCRs) play critical roles in diverse neurobiological processes including brain development, synaptogenesis, and myelination. aGPCRs have large alternatively spliced extracellular regions (ECRs) that likely mediate intercellular signaling; however, the precise roles of ECRs remain unclear. The aGPCR GPR56/ADGRG1 regulates both oligodendrocyte and cortical development. Accordingly, human GPR56 mutations cause myelination defects and brain malformations. Here, we determined the crystal structure of the GPR56 ECR, the first structure of any complete aGPCR ECR, in complex with an inverse-agonist monobody, revealing a GPCR-Autoproteolysis-Inducing domain and a previously unidentified domain that we term Pentraxin/Laminin/neurexin/sex-hormone-binding-globulin-Like (PLL). Strikingly, PLL domain deletion caused increased signaling and characterizes a GPR56 splice variant. Finally, we show that an evolutionarily conserved residue in the PLL domain is critical for oligodendrocyte development in vivo. Thus, our results suggest that the GPR56 ECR has unique and multifaceted regulatory functions, providing novel insights into aGPCR roles in neurobiology.
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