Astrocyte-secreted glypican 4 regulates release of neuronal pentraxin 1 from axons to induce functional synapse formation
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...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2017
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| _version_ | 1797097639621165056 |
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| author | Farhy-Tselnicker, I Van Casteren, A Lee, A Chang, V Aricescu, A Allen, N |
| author_facet | Farhy-Tselnicker, I Van Casteren, A Lee, A Chang, V Aricescu, A Allen, N |
| author_sort | Farhy-Tselnicker, I |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T04:58:20Z |
| format | Journal article |
| id | oxford-uuid:d763ee05-ba52-46e7-9f5e-e1dcf3a6ae2a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:58:20Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:d763ee05-ba52-46e7-9f5e-e1dcf3a6ae2a2022-03-27T08:40:46ZAstrocyte-secreted glypican 4 regulates release of neuronal pentraxin 1 from axons to induce functional synapse formationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d763ee05-ba52-46e7-9f5e-e1dcf3a6ae2aEnglishSymplectic Elements at OxfordElsevier2017Farhy-Tselnicker, IVan Casteren, ALee, AChang, VAricescu, AAllen, NThe 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. |
| spellingShingle | Farhy-Tselnicker, I Van Casteren, A Lee, A Chang, V Aricescu, A Allen, N Astrocyte-secreted glypican 4 regulates release of neuronal pentraxin 1 from axons to induce functional synapse formation |
| title | Astrocyte-secreted glypican 4 regulates release of neuronal pentraxin 1 from axons to induce functional synapse formation |
| title_full | Astrocyte-secreted glypican 4 regulates release of neuronal pentraxin 1 from axons to induce functional synapse formation |
| title_fullStr | Astrocyte-secreted glypican 4 regulates release of neuronal pentraxin 1 from axons to induce functional synapse formation |
| title_full_unstemmed | Astrocyte-secreted glypican 4 regulates release of neuronal pentraxin 1 from axons to induce functional synapse formation |
| title_short | Astrocyte-secreted glypican 4 regulates release of neuronal pentraxin 1 from axons to induce functional synapse formation |
| title_sort | astrocyte secreted glypican 4 regulates release of neuronal pentraxin 1 from axons to induce functional synapse formation |
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