ArticleNature2012
Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 436 papers.
What it found
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Who cites it
436 citing papers in PubMed, 746 citations in OpenAlex.
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- ATP13A4 gates extracellular polyamine levels to control excitatory synaptogenesis.Nature communications · 2026Article
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- Astrocyte-driven multicellular mechanisms of CNS repair and cerebroprotection.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- GPC6 facilitates progression of SHH-subgroup medulloblastoma by enhancing Hedgehog secretion and signaling responses.Journal of biomedical research · 2026Article
- Chronic ethanol drinking alters medial prefrontal cortex and nucleus accumbens astrocyte translatome and extracellular matrix glycosaminoglycans.Neuropharmacology · 2026Article
- PTP1B in astrocytes drives pathogen-induced neurodegeneration.Journal of neuroinflammation · 2026Article
- Polysialic Acid Modulation of Glutamate Receptors and Synaptic Mechanisms Underlying Neuronal Plasticity.NeuroSci · 2026Review
- TREM2-mediated microglial phagocytosis of inhibitory synapses contributes to prolonged FS-induced epileptogenesis.Cell death discovery · 2026Article
- Mesoscale molecular architecture of the human striatum across cell types and lifespan.bioRxiv : the preprint server for biology · 2026Article
- Synaptic control of retinal ganglion cell survival and axon regeneration.Molecular neurodegeneration · 2026Review
- Senescent Astrocytes: A New Player in Brain Aging and Cognitive Decline.Brain sciences · 2026Review
- Radial-glia-to-astrocyte trans-differentiation and astrocyte transcriptional convergence are coordinated by CEH-43/DLX inbioRxiv : the preprint server for biology · 2026Article
- Astrocytes and Alcohol Throughout the Lifespan.Biological psychiatry · 2026Review
- Does Altered Membrane Glycosylation Contribute to Neurodevelopmental Dysfunction in Autism Spectrum Disorder?Membranes · 2026Review
376 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
In the developing central nervous system (CNS), the control of synapse number and function is critical to the formation of neural circuits. We previously demonstrated that astrocyte-secreted factors powerfully induce the formation of functional excitatory synapses between CNS neurons. Astrocyte-secreted thrombospondins induce the formation of structural synapses, but these synapses are postsynaptically silent. Here we use biochemical fractionation of astrocyte-conditioned medium to identify glypican 4 (Gpc4) and glypican 6 (Gpc6) as astrocyte-secreted signals sufficient to induce functional synapses between purified retinal ganglion cell neurons, and show that depletion of these molecules from astrocyte-conditioned medium significantly reduces its ability to induce postsynaptic activity. Application of Gpc4 to purified neurons is sufficient to increase the frequency and amplitude of glutamatergic synaptic events. This is achieved by increasing the surface level and clustering, but not overall cellular protein level, of the GluA1 subunit of the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) glutamate receptor (AMPAR). Gpc4 and Gpc6 are expressed by astrocytes in vivo in the developing CNS, with Gpc4 expression enriched in the hippocampus and Gpc6 enriched in the cerebellum. Finally, we demonstrate that Gpc4-deficient mice have defective synapse formation, with decreased amplitude of excitatory synaptic currents in the developing hippocampus and reduced recruitment of AMPARs to synapses. These data identify glypicans as a family of novel astrocyte-derived molecules that are necessary and sufficient to promote glutamate receptor clustering and receptivity and to induce the formation of postsynaptically functioning CNS synapses.
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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.