ArticleCommunications biology2020
Synaptamide activates the adhesion GPCR GPR110 (ADGRF1) through GAIN domain binding.
Article in Communications biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- The therapeutic potential of orphan adhesion G-protein-coupled receptors.Nature reviews. Drug discovery · 2026Review
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- Effects of GPR110 expression on neurobehavioral outcomes in mice.Frontiers in neuroscience · 2026Article
- Hepatic GPR110 contributes to sex disparity in the development of MASH through oestrogen receptor α-dependent signalling.Nature metabolism · 2026Article
- Adhesion G-Protein Coupled Receptors in Neurological and Psychiatric Disorders.Journal of psychiatry and brain science · 2025Article
- Pharmacological potential of endocannabinoid and endocannabinoid-like compounds in protecting intestinal structure and metabolism under high-fat conditions.Frontiers in pharmacology · 2025Review
- Roadmap for the expression of canonical and extended endocannabinoid system receptors and metabolic enzymes in peripheral organs of preclinical animal models.Physiological reports · 2024Article
- Anti-Inflammatory Effect of Synaptamide in Ischemic Acute Kidney Injury and the Role of G-Protein-Coupled Receptor 110.International journal of molecular sciences · 2024Article
- Interaction between GPR110 (ADGRF1) and tight junction protein occludin implicated in blood-brain barrier permeability.iScience · 2023Article
- Ligand-Induced Activation of GPR110 (ADGRF1) to Improve Visual Function Impaired by Optic Nerve Injury.International journal of molecular sciences · 2023Article
- Adhesion G protein-coupled receptors: structure, signaling, physiology, and pathophysiology.Physiological reviews · 2022Review
- Structural basis of adhesion GPCR GPR110 activation by stalk peptide and G-proteins coupling.Nature communications · 2022Article
- Molecular and Signaling Mechanisms for Docosahexaenoic Acid-Derived Neurodevelopment and Neuroprotection.International journal of molecular sciences · 2022Review
- Article
- The GPCR properties of polycystin-1- A new paradigm.Frontiers in molecular biosciences · 2022Review
- Anti-Inflammatory Activity ofInternational journal of molecular sciences · 2021Article
- Emerging roles of adhesion G protein-coupled receptors.Biochemical Society transactions · 2021Review
- GPR110 ligands reduce chronic optic tract gliosis and visual deficit following repetitive mild traumatic brain injury in mice.Journal of neuroinflammation · 2021Article
- A novel role of ADGRF1 (GPR110) in promoting cellular quiescence and chemoresistance in human epidermal growth factor receptor 2-positive breast cancer.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Ligand-Induced GPR110 Activation Facilitates Axon Growth after Injury.International journal of molecular sciences · 2021Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Adhesion G protein-coupled receptors (aGPCR) are characterized by a large extracellular region containing a conserved GPCR-autoproteolysis-inducing (GAIN) domain. Despite their relevance to several disease conditions, we do not understand the molecular mechanism by which aGPCRs are physiologically activated. GPR110 (ADGRF1) was recently deorphanized as the functional receptor of N-docosahexaenoylethanolamine (synaptamide), a potent synaptogenic metabolite of docosahexaenoic acid. Thus far, synaptamide is the first and only small-molecule endogenous ligand of an aGPCR. Here, we demonstrate the molecular basis of synaptamide-induced activation of GPR110 in living cells. Using in-cell chemical cross-linking/mass spectrometry, computational modeling and mutagenesis-assisted functional assays, we discover that synaptamide specifically binds to the interface of GPR110 GAIN subdomains through interactions with residues Q511, N512 and Y513, causing an intracellular conformational change near TM6 that triggers downstream signaling. This ligand-induced GAIN-targeted activation mechanism provides a framework for understanding the physiological function of aGPCRs and therapeutic targeting in the GAIN domain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.