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The small GTPase ARF6 regulates GABAergic synapse development
ADP ribosylation factors (ARFs) are a family of small GTPases composed of six members (ARF1–6) that control various cellular functions, including membrane trafficking and actin cytoskeletal rearrangement, in eukaryotic cells. Among them, ARF1 and ARF6 are the most studied in neurons, particularly at...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945580/ https://www.ncbi.nlm.nih.gov/pubmed/31907062 http://dx.doi.org/10.1186/s13041-019-0543-3 |
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author | Kim, Hyeonho Jung, Hyeji Jung, Hyunsu Kwon, Seok-Kyu Ko, Jaewon Um, Ji Won |
author_facet | Kim, Hyeonho Jung, Hyeji Jung, Hyunsu Kwon, Seok-Kyu Ko, Jaewon Um, Ji Won |
author_sort | Kim, Hyeonho |
collection | PubMed |
description | ADP ribosylation factors (ARFs) are a family of small GTPases composed of six members (ARF1–6) that control various cellular functions, including membrane trafficking and actin cytoskeletal rearrangement, in eukaryotic cells. Among them, ARF1 and ARF6 are the most studied in neurons, particularly at glutamatergic synapses, but their roles at GABAergic synapses have not been investigated. Here, we show that a subset of ARF6 protein is localized at GABAergic synapses in cultured hippocampal neurons. In addition, we found that knockdown (KD) of ARF6, but not ARF1, triggered a reduction in the number of GABAergic synaptic puncta in mature cultured neurons in an ARF activity-dependent manner. ARF6 KD also reduced GABAergic synaptic density in the mouse hippocampal dentate gyrus (DG) region. Furthermore, ARF6 KD in the DG increased seizure susceptibility in an induced epilepsy model. Viewed together, our results suggest that modulating ARF6 and its regulators could be a therapeutic strategy against brain pathologies involving hippocampal network dysfunction, such as epilepsy. |
format | Online Article Text |
id | pubmed-6945580 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-69455802020-01-07 The small GTPase ARF6 regulates GABAergic synapse development Kim, Hyeonho Jung, Hyeji Jung, Hyunsu Kwon, Seok-Kyu Ko, Jaewon Um, Ji Won Mol Brain Research ADP ribosylation factors (ARFs) are a family of small GTPases composed of six members (ARF1–6) that control various cellular functions, including membrane trafficking and actin cytoskeletal rearrangement, in eukaryotic cells. Among them, ARF1 and ARF6 are the most studied in neurons, particularly at glutamatergic synapses, but their roles at GABAergic synapses have not been investigated. Here, we show that a subset of ARF6 protein is localized at GABAergic synapses in cultured hippocampal neurons. In addition, we found that knockdown (KD) of ARF6, but not ARF1, triggered a reduction in the number of GABAergic synaptic puncta in mature cultured neurons in an ARF activity-dependent manner. ARF6 KD also reduced GABAergic synaptic density in the mouse hippocampal dentate gyrus (DG) region. Furthermore, ARF6 KD in the DG increased seizure susceptibility in an induced epilepsy model. Viewed together, our results suggest that modulating ARF6 and its regulators could be a therapeutic strategy against brain pathologies involving hippocampal network dysfunction, such as epilepsy. BioMed Central 2020-01-06 /pmc/articles/PMC6945580/ /pubmed/31907062 http://dx.doi.org/10.1186/s13041-019-0543-3 Text en © The Author(s). 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Kim, Hyeonho Jung, Hyeji Jung, Hyunsu Kwon, Seok-Kyu Ko, Jaewon Um, Ji Won The small GTPase ARF6 regulates GABAergic synapse development |
title | The small GTPase ARF6 regulates GABAergic synapse development |
title_full | The small GTPase ARF6 regulates GABAergic synapse development |
title_fullStr | The small GTPase ARF6 regulates GABAergic synapse development |
title_full_unstemmed | The small GTPase ARF6 regulates GABAergic synapse development |
title_short | The small GTPase ARF6 regulates GABAergic synapse development |
title_sort | small gtpase arf6 regulates gabaergic synapse development |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945580/ https://www.ncbi.nlm.nih.gov/pubmed/31907062 http://dx.doi.org/10.1186/s13041-019-0543-3 |
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