ArticleNeuron2018
An Input-Specific Orphan Receptor GPR158-HSPG Interaction Organizes Hippocampal Mossy Fiber-CA3 Synapses.
Article in Neuron, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 79 citations in OpenAlex.
- Pleiotrophin regulates presynaptic assembly and function through heparan sulfate-dependent binding to neurexin1.Cell reports · 2026Article
- Cognitive Deficits in Female GPR158 Knockout Mice Revealed by Automated Home-Cage Testing.Genes, brain, and behavior · 2026Article
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- In situ proteomics unveils specialized domains for extrasynaptic signaling on neuronal cilia.Science advances · 2026Article
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- Targeting mGlyR with nanobodies for depression.Nature communications · 2026Article
- A dynamic gene regulatory code drives synaptic development of hippocampal granule cells.Science advances · 2025Article
- The diverse roles of complex glycans in synapse development and function.Current opinion in neurobiology · 2025Review
- Astrocyte glypican 5 regulates synapse maturation and stabilization.Cell reports · 2025Article
- Osteocalcin and GPR158: linking bone and brain function.Frontiers in cell and developmental biology · 2025Review
- Emerging modes of regulation of neuromodulatory G protein-coupled receptors.Trends in neurosciences · 2024Review
- Glycine-induced activation of GPR158 increases the intrinsic excitability of medium spiny neurons in the nucleus accumbens.Cellular and molecular life sciences : CMLS · 2024Article
- Cell Adhesion Molecule Signaling at the Synapse: Beyond the Scaffold.Cold Spring Harbor perspectives in biology · 2024Review
- Structural and functional characterization of the IgSF21-neurexin2α complex and its related signaling pathways in the regulation of inhibitory synapse organization.Frontiers in molecular neuroscience · 2024Article
- Article
- Expression Mapping and Functional Analysis of Orphan G-Protein-Coupled Receptor GPR158 in the Adult Mouse Brain Using a GPR158 Transgenic Mouse.Biomolecules · 2023Article
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- Article
- Review
- Cryo-EM structure of human GPR158 receptor coupled to the RGS7-Gβ5 signaling complex.Science (New York, N.Y.) · 2022Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Pyramidal neuron dendrites integrate synaptic input from multiple partners. Different inputs converging on the same dendrite have distinct structural and functional features, but the molecular mechanisms organizing input-specific properties are poorly understood. We identify the orphan receptor GPR158 as a binding partner for the heparan sulfate proteoglycan (HSPG) glypican 4 (GPC4). GPC4 is enriched on hippocampal granule cell axons (mossy fibers), whereas postsynaptic GPR158 is restricted to the proximal segment of CA3 apical dendrites receiving mossy fiber input. GPR158-induced presynaptic differentiation in contacting axons requires cell-surface GPC4 and the co-receptor LAR. Loss of GPR158 increases mossy fiber synapse density but disrupts bouton morphology, impairs ultrastructural organization of active zone and postsynaptic density, and reduces synaptic strength of this connection, while adjacent inputs on the same dendrite are unaffected. Our work identifies an input-specific HSPG-GPR158 interaction that selectively organizes synaptic architecture and function of developing mossy fiber-CA3 synapses in the hippocampus.
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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.