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cAMP-EPAC-Dependent Regulation of Gephyrin Phosphorylation and GABA(A)R Trapping at Inhibitory Synapses
GABA(A) and glycine receptors are thought to compete for gephyrin-binding sites at mixed inhibitory synapses. Changes in the occupancy of one receptor type are therefore expected to have opposite effects on the clustering of the other receptors. This does not explain, however, whether different rece...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6926171/ https://www.ncbi.nlm.nih.gov/pubmed/31835170 http://dx.doi.org/10.1016/j.isci.2019.11.013 |
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author | Niwa, Fumihiro Patrizio, Angela Triller, Antoine Specht, Christian G. |
author_facet | Niwa, Fumihiro Patrizio, Angela Triller, Antoine Specht, Christian G. |
author_sort | Niwa, Fumihiro |
collection | PubMed |
description | GABA(A) and glycine receptors are thought to compete for gephyrin-binding sites at mixed inhibitory synapses. Changes in the occupancy of one receptor type are therefore expected to have opposite effects on the clustering of the other receptors. This does not explain, however, whether different receptors can be regulated independently from one another. Here we show that cAMP-dependent signaling reduces gephyrin phosphorylation at residue S270 in spinal cord neurons. Although no ultrastructural changes of the synaptic scaffold were detected using super-resolution imaging, gephyrin de-phosphorylation was associated with a selective increase in GABA(A)R diffusion and the loss of the receptors from synapses. As opposed to the PKA-dependent dispersal of α3-containing GlyRs, the regulation of gephyrin phosphorylation and GABA(A)R dynamics acts via non-canonical EPAC signaling. Subtype-specific changes in receptor mobility can thus differentially contribute to changes in inhibitory synaptic strength, such as the disinhibition of spinal cord neurons during inflammatory processes. |
format | Online Article Text |
id | pubmed-6926171 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-69261712019-12-30 cAMP-EPAC-Dependent Regulation of Gephyrin Phosphorylation and GABA(A)R Trapping at Inhibitory Synapses Niwa, Fumihiro Patrizio, Angela Triller, Antoine Specht, Christian G. iScience Article GABA(A) and glycine receptors are thought to compete for gephyrin-binding sites at mixed inhibitory synapses. Changes in the occupancy of one receptor type are therefore expected to have opposite effects on the clustering of the other receptors. This does not explain, however, whether different receptors can be regulated independently from one another. Here we show that cAMP-dependent signaling reduces gephyrin phosphorylation at residue S270 in spinal cord neurons. Although no ultrastructural changes of the synaptic scaffold were detected using super-resolution imaging, gephyrin de-phosphorylation was associated with a selective increase in GABA(A)R diffusion and the loss of the receptors from synapses. As opposed to the PKA-dependent dispersal of α3-containing GlyRs, the regulation of gephyrin phosphorylation and GABA(A)R dynamics acts via non-canonical EPAC signaling. Subtype-specific changes in receptor mobility can thus differentially contribute to changes in inhibitory synaptic strength, such as the disinhibition of spinal cord neurons during inflammatory processes. Elsevier 2019-11-09 /pmc/articles/PMC6926171/ /pubmed/31835170 http://dx.doi.org/10.1016/j.isci.2019.11.013 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Niwa, Fumihiro Patrizio, Angela Triller, Antoine Specht, Christian G. cAMP-EPAC-Dependent Regulation of Gephyrin Phosphorylation and GABA(A)R Trapping at Inhibitory Synapses |
title | cAMP-EPAC-Dependent Regulation of Gephyrin Phosphorylation and GABA(A)R Trapping at Inhibitory Synapses |
title_full | cAMP-EPAC-Dependent Regulation of Gephyrin Phosphorylation and GABA(A)R Trapping at Inhibitory Synapses |
title_fullStr | cAMP-EPAC-Dependent Regulation of Gephyrin Phosphorylation and GABA(A)R Trapping at Inhibitory Synapses |
title_full_unstemmed | cAMP-EPAC-Dependent Regulation of Gephyrin Phosphorylation and GABA(A)R Trapping at Inhibitory Synapses |
title_short | cAMP-EPAC-Dependent Regulation of Gephyrin Phosphorylation and GABA(A)R Trapping at Inhibitory Synapses |
title_sort | camp-epac-dependent regulation of gephyrin phosphorylation and gaba(a)r trapping at inhibitory synapses |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6926171/ https://www.ncbi.nlm.nih.gov/pubmed/31835170 http://dx.doi.org/10.1016/j.isci.2019.11.013 |
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