ArticleNeuron2013
Unbiased discovery of glypican as a receptor for LRRTM4 in regulating excitatory synapse development.
Article in Neuron, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 166 citations in OpenAlex.
- Ternary Neurexin-T178-PTPR complexes represent a pre-synaptic core-module of neuronal synapse organization.Nature communications · 2026Article
- Pleiotrophin regulates presynaptic assembly and function through heparan sulfate-dependent binding to neurexin1.Cell reports · 2026Article
- A decade of progress in understanding LRRTM and Slitrk synaptic cell-adhesion molecules.Molecules and cells · 2026Review
- Does Altered Membrane Glycosylation Contribute to Neurodevelopmental Dysfunction in Autism Spectrum Disorder?Membranes · 2026Review
- MMP2 sheds Glypican-4 to suppress Slit3-Robo4 signaling and angiogenesis.Proteoglycan research · 2026Article
- MeCP2 regulates telencephalic development in human cerebral organoids.Cell reports · 2025Article
- Comparative Single-Cell Transcriptome Analysis of c-Met Receptor Expressing and Non-Expressing Projection Neurons in the Developing Frontal and Visual Cortices.Developmental neuroscience · 2025Article
- β-Amyloid induces microglial expression of GPC4 and APOE leading to increased neuronal tau pathology and toxicity.Molecular neurodegeneration · 2025Article
- An integrated transcriptomic and proteomic map of the mouse hippocampus at synaptic resolution.Nature communications · 2025Article
- Early Locus Coeruleus noradrenergic axon loss drives olfactory dysfunction in Alzheimer's disease.Nature communications · 2025Article
- High-content image-based pooled screens reveal regulators of synaptogenesis.Cell reports · 2025Article
- A synthetic HS structure selectively impairs the morphology and function of excitatory synapse by disrupting neurexin1 interactions.Glycobiology · 2025Article
- High-affinity detection of biotinylated endogenous neuroligin-1 at excitatory and inhibitory synapses using a tagged knock-in mouse.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Astrocyte glypican 5 regulates synapse maturation and stabilization.Cell reports · 2025Article
- Synaptic signatures and disease vulnerabilities of layer 5 pyramidal neurons.Nature communications · 2025Article
- Cellular and Molecular Mechanisms Regulating Retinal Synapse Development.Annual review of vision science · 2024Review
- Glioblastoma disrupts cortical network activity at multiple spatial and temporal scales.Nature communications · 2024Article
- Cell Adhesion Molecule Signaling at the Synapse: Beyond the Scaffold.Cold Spring Harbor perspectives in biology · 2024Review
- Article
- Concerted neuron-astrocyte gene expression declines in aging and schizophrenia.bioRxiv : the preprint server for biology · 2024Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Leucine-rich repeat (LRR) proteins have recently been identified as important regulators of synapse development and function, but for many LRR proteins the ligand-receptor interactions are not known. Here we identify the heparan sulfate (HS) proteoglycan glypican as a receptor for LRRTM4 using an unbiased proteomics-based approach. Glypican binds LRRTM4, but not LRRTM2, in an HS-dependent manner. Glypican 4 (GPC4) and LRRTM4 localize to the pre- and postsynaptic membranes of excitatory synapses, respectively. Consistent with a trans-synaptic interaction, LRRTM4 triggers GPC4 clustering in contacting axons and GPC4 induces clustering of LRRTM4 in contacting dendrites in an HS-dependent manner. LRRTM4 positively regulates excitatory synapse development in cultured neurons and in vivo, and the synaptogenic activity of LRRTM4 requires the presence of HS on the neuronal surface. Our results identify glypican as an LRRTM4 receptor and indicate that a trans-synaptic glypican-LRRTM4 interaction regulates excitatory synapse development.
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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.