ArticleProceedings of the National Academy of Sciences of the United States of America2018
Synaptic adhesion protein ELFN1 is a selective allosteric modulator of group III metabotropic glutamate receptors
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Genomic Analysis Identifies Risk Factors in Restless Legs Syndrome.Annals of neurology · 2024Pooled it
- Structural basis for modulation of group III mGlu receptors by transsynaptic interactions.Science advances · 2026Article
- Deep single-cell decoding of human pancreatic islets reveals T2D β-cell gene expression defects.The EMBO journal · 2026Article
- N-Glycosylation of mGluR6 Modulates Receptor Cell-Surface Transport, G-Protein Coupling, and Interactions With Synaptic Adhesion Molecules.Journal of molecular neuroscience : MN · 2026Article
- mGluR4-NPDC1 complex mediates α-synuclein fibril-induced neurodegeneration.Nature communications · 2025Article
- Single-Cell Multi-Modal Differential Analysis of the Human Neo-Cortex in HIV Infection Reveals Similarities with Hallmarks of Alzheimer's Disease.Research square · 2025Article
- Trans-synaptic Interaction with mGluR6 Contributes to ELFN1 Presynaptic Enrichment in Rod Photoreceptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Domain coupling in activation of a family C GPCR.Nature chemical biology · 2025Article
- DeFrND: detergent-free reconstitution into native nanodiscs with designer membrane scaffold peptides.Nature communications · 2025Article
- Profiling the Impact of mGluACS chemical neuroscience · 2025Article
- Homeostatic scaling of dynorphin signaling by a non-canonical opioid receptor.Nature communications · 2025Article
- [High expression of ELFN1 is a prognostic biomarker and promotes proliferation and metastasis of colorectal cancer cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Molecular mechanism establishing the OFF pathway in vision.Nature communications · 2025Article
- Trans-synaptic modulation of cholinergic circuits tunes opioid reinforcement.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Defective glycosylation and ELFN1 binding of mGluR6 congenital stationary night blindness mutants.Life science alliance · 2025Article
- Pan-cancer analysis reveals ELFN1 as a novel prognostic biomarker and immunotherapeutic target associated with tumor microenvironment remodeling and promoting malignant phenotypes in colorectal cancer.Frontiers in oncology · 2025Article
- Distinct autoregulatory roles of ELFN1 intracellular and extracellular domains on membrane trafficking, synaptic localization, and dimerization.The Journal of biological chemistry · 2025Article
- Cellular and Molecular Mechanisms Regulating Retinal Synapse Development.Annual review of vision science · 2024Review
- Emerging modes of regulation of neuromodulatory G protein-coupled receptors.Trends in neurosciences · 2024Review
- Monoallelic de novoScience advances · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Functional characterization of the GPCR interactome has been focused predominantly on intracellular interactions, yet GPCRs are increasingly found in complex with extracellular proteins. Extracellular leucine-rich repeat fibronectin type III domain containing 1 (ELFN1) was recently reported to physically anchor mGluR6 and mGluR7 across retinal and hippocampal synapses, respectively; however, the consequence of transsynaptic interactions on properties and pharmacology of these receptors are unknown. In the current study, we explore the effects of ELFN1 on mGluR signaling and pharmacology. First, we established the binding specificity of ELFN1 and found it to be recruited selectively to all group III mGluRs (mGluR4, mGluR6, mGluR7, and mGluR8), but not other mGluR species. Using site-directed mutagenesis we mapped binding determinants of this interaction to two distinct sites on the ELFN1 ectodomain. To evaluate functional aspects of the interaction, we developed a transcellular signaling assay in reconstituted HEK293 cells which monitors changes in mGluR activity in one cell following its exposure to separate ELFN1-containing cells. Using this platform, we found that ELFN1 acts as an allosteric modulator of class III mGluR activity in suppressing cAMP accumulation: altering both agonist-induced and constitutive receptor activity. Using bioluminescence resonance energy transfer-based real-time kinetic assays, we established that ELFN1 alters the ability of mGluRs to activate G proteins. Our findings demonstrate that core properties of class III mGluRs can be altered via extracellular interactions with ELFN1 which serves as a transsynaptic allosteric modulator for these receptors. Furthermore, our unique assay platform opens avenues for exploring transcellular/transsynaptic pharmacology of other GPCR transcomplexes.
Indexed as
Identifiers
What OpenQuestion holds
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.