Astrocyte-Secreted Glypican 4 Regulates Release of Neuronal Pentraxin 1 from Axons to Induce Functional Synapse Formation
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The generation of precise synaptic connections between developing neurons is critical to the formation of functional neural circuits. Astrocyte-secreted glypican 4 induces formation of active excitatory synapses by recruiting AMPA glutamate receptors to the postsynaptic cell surface. We now identify the molecular mechanism of how glypican 4 exerts its effect. Glypican 4 induces release of the AMPA receptor clustering factor neuronal pentraxin 1 from presynaptic terminals by signaling through presynaptic protein tyrosine phosphatase receptor δ. Pentraxin then accumulates AMPA receptors on the postsynaptic terminal forming functional synapses. Our findings reveal a signaling pathway that regulates synaptic activity during central nervous system development and demonstrates a role for astrocytes as organizers of active synaptic connections by coordinating both pre and post synaptic neurons. As mutations in glypicans are associated with neurological disorders, such as autism and schizophrenia, this signaling cascade offers new avenues to modulate synaptic function in disease.
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NPTXs play a role in synaptogenesis.
“NPTXs play a role in synaptogenesis (Farhy-Tselnicker et al. 2017; Figueiro-Silva et al. 2015; Sia et al. 2007)”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Farhy-Tselnicker et al. 2017
Astrocyte-secreted GPC4 induces NPTX1 release from pre-synaptic terminals through RPTPδ.
“New data suggested astrocyte-secreted glypican-4 (GPC4) to induce NPTX1 release from pre-synaptic terminals through type 2a receptor protein tyrosine phosphatase (RPTPδ) (Farhy-Tselnicker et al. 2017)”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Farhy-Tselnicker et al. 2017
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- Authors
- Farhy-Tselnicker, I., van Casteren, A. C. M., Lee, A., Chang, V. T., Aricescu, A. R., & Allen, N. J.
- Affiliations
- Salk Institute for Biological Studies (US)
- Centre for Human Genetics (GB)
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Allen, Nicola J.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2017-10
- Volume
- 96
- Issue
- 2
- Pages
- 428-445.e13
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC5663462
- OpenAlex
- W2764189104
- Cited by
- 199
- References
- 61
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 27 · 2023: 22 · 2022: 22 · 2021: 37 · 2020: 29 · 2019: 12 · 2018: 15 · 2017: 2
- FWCI
- 7.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuron (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- NIH-NINDS (R01 NS089791, P30 NS072031)
- Hearst
- Pew
- Ellison
- Dana
- Whitehall Foundations
- Larry and Carol Greenfield
- Catarina Foundation
- Wellcome Trust
- UK Medical Research Council (L009609, MC_UP_1201/15)
- Core Facilities of the Salk Institute
- NIH-NCI (CCSG P30 014195)
- Waitt Foundation
- Wellcome Trust Centre for Human Genetics (090532/Z/09/Z)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- GPC4, astrocytes, synaptogenesis, presynaptic terminals, excitatory synapses, synaptic development, glypicans, autism spectrum disorder, schizophrenia
- MeSH terms
- Pentraxins, Amino Acid Sequence, Animals, Astrocytes, Axons, C-Reactive Protein, Cells, Cultured, Female, Humans, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Retinal Ganglion Cells, Synapses, Rats, Sprague-Dawley, Receptors, AMPA, Mice, Knockout, Heparan Sulfate Proteoglycans, Mice, Rats, Glypicans, HEK293 Cells
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