ArticleeNeuro
Heparan Sulfated Glypican-4 Is Released from Astrocytes by Proteolytic Shedding and GPI-Anchor Cleavage Mechanisms.
Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- Prognostic value of circulating glypican-4 in chronic heart failure.Journal of molecular medicine (Berlin, Germany) · 2026Article
- MMP2 sheds Glypican-4 to suppress Slit3-Robo4 signaling and angiogenesis.Proteoglycan research · 2026Article
- Roles of Glia in Synapse Nano-organization.Advances in neurobiology · 2026Review
- Heparan sulphate and neural development: dissecting the roles of astrocyte-expressed heparan sulphate.Biochemical Society transactions · 2025Review
- β-Amyloid induces microglial expression of GPC4 and APOE leading to increased neuronal tau pathology and toxicity.Molecular neurodegeneration · 2025Article
- Heparan Sulfate Proteoglycans as Potential Markers for In Vitro Human Neural Lineage Specification.Cells · 2025Article
- Identifying potential biomarkers in the hippocampus of chronic fatigue syndrome rats treated with moxibustion at Zusanli (ST36): a proteomics study.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- Substrate O-glycosylation actively regulates extracellular proteolysis.Protein science : a publication of the Protein Society · 2024Article
- Astrocyte Regulation of Synapse Formation, Maturation, and Elimination.Cold Spring Harbor perspectives in biology · 2024Review
- Beyond amyloid and tau: rethinking Alzheimer's disease through less explored avenues.Open biology · 2024Review
- (Patho)Physiology of Glycosylphosphatidylinositol-Anchored Proteins I: Localization at Plasma Membranes and Extracellular Compartments.Biomolecules · 2023Review
- Extracellular matrix and synapse formation.Bioscience reports · 2023Article
- Proteolysis: a key post-translational modification regulating proteoglycans.American journal of physiology. Cell physiology · 2022Review
- Evaluation of the association of serum glypican-4 with prevalent and future kidney function.Scientific reports · 2022Article
- Circulating syndecan-1 and glypican-4 predict 12-month survival in metastatic colorectal cancer patients.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Astrocytes provide neurons with diffusible factors that promote synapse formation and maturation. In particular, glypican-4/GPC4 released from astrocytes promotes the maturation of excitatory synapses. Unlike other secreted factors, GPC4 contains the C-terminal GPI-anchorage signal. However, the mechanism by which membrane-tethered GPC4 is released from astrocytes is unknown. Using mouse primary astrocyte cultures and a quantitative luciferase-based release assay, we show that GPC4 is expressed on the astrocyte surface via a GPI-anchorage. Soluble GPC4 is robustly released from the astrocytes largely by proteolytic shedding and, to a lesser extent, by GPI-anchor cleavage, but not by vesicular release. Pharmacological, overexpression, and loss of function screens showed that ADAM9 in part mediates the release of GPC4 from astrocytes. The released GPC4 contains the heparan sulfate side chain, suggesting that these release mechanisms provide the active form that promotes synapse maturation and function. Overall, our studies identified the release mechanisms and the major releasing enzyme of GPC4 in astrocytes and will provide insights into understanding how astrocytes regulate synapse formation and maturation.
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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.