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Tuning GABAergic Inhibition: Gephyrin Molecular Organization and Functions
To be highly reliable, synaptic transmission needs postsynaptic receptors (Rs) in precise apposition to the presynaptic release sites. At inhibitory synapses, the postsynaptic protein gephyrin self-assembles to form a scaffold that anchors glycine and GABA(A)Rs to the cytoskeleton, thus ensuring the...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351109/ https://www.ncbi.nlm.nih.gov/pubmed/31356900 http://dx.doi.org/10.1016/j.neuroscience.2019.07.036 |
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author | Pizzarelli, Rocco Griguoli, Marilena Zacchi, Paola Petrini, Enrica Maria Barberis, Andrea Cattaneo, Antonino Cherubini, Enrico |
author_facet | Pizzarelli, Rocco Griguoli, Marilena Zacchi, Paola Petrini, Enrica Maria Barberis, Andrea Cattaneo, Antonino Cherubini, Enrico |
author_sort | Pizzarelli, Rocco |
collection | PubMed |
description | To be highly reliable, synaptic transmission needs postsynaptic receptors (Rs) in precise apposition to the presynaptic release sites. At inhibitory synapses, the postsynaptic protein gephyrin self-assembles to form a scaffold that anchors glycine and GABA(A)Rs to the cytoskeleton, thus ensuring the accurate accumulation of postsynaptic receptors at the right place. This protein undergoes several post-translational modifications which control protein–protein interaction and downstream signaling pathways. In addition, through the constant exchange of scaffolding elements and receptors in and out of synapses, gephyrin dynamically regulates synaptic strength and plasticity. The aim of the present review is to highlight recent findings on the functional role of gephyrin at GABAergic inhibitory synapses. We will discuss different approaches used to interfere with gephyrin in order to unveil its function. In addition, we will focus on the impact of gephyrin structure and distribution at the nanoscale level on the functional properties of inhibitory synapses as well as the implications of this scaffold protein in synaptic plasticity processes. Finally, we will emphasize how gephyrin genetic mutations or alterations in protein expression levels are implicated in several neuropathological disorders, including autism spectrum disorders, schizophrenia, temporal lobe epilepsy and Alzheimer's disease, all associated with severe deficits of GABAergic signaling. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries. |
format | Online Article Text |
id | pubmed-7351109 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-73511092020-07-15 Tuning GABAergic Inhibition: Gephyrin Molecular Organization and Functions Pizzarelli, Rocco Griguoli, Marilena Zacchi, Paola Petrini, Enrica Maria Barberis, Andrea Cattaneo, Antonino Cherubini, Enrico Neuroscience Article To be highly reliable, synaptic transmission needs postsynaptic receptors (Rs) in precise apposition to the presynaptic release sites. At inhibitory synapses, the postsynaptic protein gephyrin self-assembles to form a scaffold that anchors glycine and GABA(A)Rs to the cytoskeleton, thus ensuring the accurate accumulation of postsynaptic receptors at the right place. This protein undergoes several post-translational modifications which control protein–protein interaction and downstream signaling pathways. In addition, through the constant exchange of scaffolding elements and receptors in and out of synapses, gephyrin dynamically regulates synaptic strength and plasticity. The aim of the present review is to highlight recent findings on the functional role of gephyrin at GABAergic inhibitory synapses. We will discuss different approaches used to interfere with gephyrin in order to unveil its function. In addition, we will focus on the impact of gephyrin structure and distribution at the nanoscale level on the functional properties of inhibitory synapses as well as the implications of this scaffold protein in synaptic plasticity processes. Finally, we will emphasize how gephyrin genetic mutations or alterations in protein expression levels are implicated in several neuropathological disorders, including autism spectrum disorders, schizophrenia, temporal lobe epilepsy and Alzheimer's disease, all associated with severe deficits of GABAergic signaling. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries. Elsevier Science 2020-07-15 /pmc/articles/PMC7351109/ /pubmed/31356900 http://dx.doi.org/10.1016/j.neuroscience.2019.07.036 Text en © 2019 The Authors 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 Pizzarelli, Rocco Griguoli, Marilena Zacchi, Paola Petrini, Enrica Maria Barberis, Andrea Cattaneo, Antonino Cherubini, Enrico Tuning GABAergic Inhibition: Gephyrin Molecular Organization and Functions |
title | Tuning GABAergic Inhibition: Gephyrin Molecular Organization and Functions |
title_full | Tuning GABAergic Inhibition: Gephyrin Molecular Organization and Functions |
title_fullStr | Tuning GABAergic Inhibition: Gephyrin Molecular Organization and Functions |
title_full_unstemmed | Tuning GABAergic Inhibition: Gephyrin Molecular Organization and Functions |
title_short | Tuning GABAergic Inhibition: Gephyrin Molecular Organization and Functions |
title_sort | tuning gabaergic inhibition: gephyrin molecular organization and functions |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351109/ https://www.ncbi.nlm.nih.gov/pubmed/31356900 http://dx.doi.org/10.1016/j.neuroscience.2019.07.036 |
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