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VGLUT1 functions as a glutamate/proton exchanger with chloride channel activity in hippocampal glutamatergic synapses
Glutamate is the major excitatory transmitter in the vertebrate nervous system. To maintain synaptic efficacy, recycling synaptic vesicles (SV) are refilled with glutamate by vesicular glutamate transporters (VGLUTs). The dynamics and mechanism of glutamate uptake in intact neurons are still largely...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741633/ https://www.ncbi.nlm.nih.gov/pubmed/29273736 http://dx.doi.org/10.1038/s41467-017-02367-6 |
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author | Martineau, Magalie Guzman, Raul E. Fahlke, Christoph Klingauf, Jürgen |
author_facet | Martineau, Magalie Guzman, Raul E. Fahlke, Christoph Klingauf, Jürgen |
author_sort | Martineau, Magalie |
collection | PubMed |
description | Glutamate is the major excitatory transmitter in the vertebrate nervous system. To maintain synaptic efficacy, recycling synaptic vesicles (SV) are refilled with glutamate by vesicular glutamate transporters (VGLUTs). The dynamics and mechanism of glutamate uptake in intact neurons are still largely unknown. Here, we show by live-cell imaging with pH- and chloride-sensitive fluorescent probes in cultured hippocampal neurons of wild-type and VGLUT1-deficient mice that in SVs VGLUT functions as a glutamate/proton exchanger associated with a channel-like chloride conductance. After endocytosis most internalized Cl(−) is substituted by glutamate in an electrically, and presumably osmotically, neutral manner, and this process is driven by both the Cl(−) gradient itself and the proton motive force provided by the vacuolar H(+)-ATPase. Our results shed light on the transport mechanism of VGLUT under physiological conditions and provide a framework for how modulation of glutamate transport via Cl(−) and pH can change synaptic strength. |
format | Online Article Text |
id | pubmed-5741633 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57416332017-12-29 VGLUT1 functions as a glutamate/proton exchanger with chloride channel activity in hippocampal glutamatergic synapses Martineau, Magalie Guzman, Raul E. Fahlke, Christoph Klingauf, Jürgen Nat Commun Article Glutamate is the major excitatory transmitter in the vertebrate nervous system. To maintain synaptic efficacy, recycling synaptic vesicles (SV) are refilled with glutamate by vesicular glutamate transporters (VGLUTs). The dynamics and mechanism of glutamate uptake in intact neurons are still largely unknown. Here, we show by live-cell imaging with pH- and chloride-sensitive fluorescent probes in cultured hippocampal neurons of wild-type and VGLUT1-deficient mice that in SVs VGLUT functions as a glutamate/proton exchanger associated with a channel-like chloride conductance. After endocytosis most internalized Cl(−) is substituted by glutamate in an electrically, and presumably osmotically, neutral manner, and this process is driven by both the Cl(−) gradient itself and the proton motive force provided by the vacuolar H(+)-ATPase. Our results shed light on the transport mechanism of VGLUT under physiological conditions and provide a framework for how modulation of glutamate transport via Cl(−) and pH can change synaptic strength. Nature Publishing Group UK 2017-12-22 /pmc/articles/PMC5741633/ /pubmed/29273736 http://dx.doi.org/10.1038/s41467-017-02367-6 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Martineau, Magalie Guzman, Raul E. Fahlke, Christoph Klingauf, Jürgen VGLUT1 functions as a glutamate/proton exchanger with chloride channel activity in hippocampal glutamatergic synapses |
title | VGLUT1 functions as a glutamate/proton exchanger with chloride channel activity in hippocampal glutamatergic synapses |
title_full | VGLUT1 functions as a glutamate/proton exchanger with chloride channel activity in hippocampal glutamatergic synapses |
title_fullStr | VGLUT1 functions as a glutamate/proton exchanger with chloride channel activity in hippocampal glutamatergic synapses |
title_full_unstemmed | VGLUT1 functions as a glutamate/proton exchanger with chloride channel activity in hippocampal glutamatergic synapses |
title_short | VGLUT1 functions as a glutamate/proton exchanger with chloride channel activity in hippocampal glutamatergic synapses |
title_sort | vglut1 functions as a glutamate/proton exchanger with chloride channel activity in hippocampal glutamatergic synapses |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741633/ https://www.ncbi.nlm.nih.gov/pubmed/29273736 http://dx.doi.org/10.1038/s41467-017-02367-6 |
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