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Molecular Basis of Coupled Transport and Anion Conduction in Excitatory Amino Acid Transporters

Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. After its release from presynaptic nerve terminals, glutamate is quickly removed from the synaptic cleft by excitatory amino acid transporters (EAATs) 1–5, a subfamily of glutamate transporters. The five prot...

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Autores principales: Alleva, Claudia, Machtens, Jan-Philipp, Kortzak, Daniel, Weyand, Ingo, Fahlke, Christoph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763778/
https://www.ncbi.nlm.nih.gov/pubmed/33587237
http://dx.doi.org/10.1007/s11064-021-03252-x
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author Alleva, Claudia
Machtens, Jan-Philipp
Kortzak, Daniel
Weyand, Ingo
Fahlke, Christoph
author_facet Alleva, Claudia
Machtens, Jan-Philipp
Kortzak, Daniel
Weyand, Ingo
Fahlke, Christoph
author_sort Alleva, Claudia
collection PubMed
description Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. After its release from presynaptic nerve terminals, glutamate is quickly removed from the synaptic cleft by excitatory amino acid transporters (EAATs) 1–5, a subfamily of glutamate transporters. The five proteins utilize a complex transport stoichiometry that couples glutamate transport to the symport of three Na(+) ions and one H(+) in exchange with one K(+) to accumulate glutamate against up to 10(6)-fold concentration gradients. They are also anion-selective channels that open and close during transitions along the glutamate transport cycle. EAATs belong to a larger family of secondary-active transporters, the SLC1 family, which also includes purely Na(+)- or H(+)-coupled prokaryotic transporters and Na(+)-dependent neutral amino acid exchangers. In recent years, molecular cloning, heterologous expression, cellular electrophysiology, fluorescence spectroscopy, structural approaches, and molecular simulations have uncovered the molecular mechanisms of coupled transport, substrate selectivity, and anion conduction in EAAT glutamate transporters. Here we review recent findings on EAAT transport mechanisms, with special emphasis on the highly conserved hairpin 2 gate, which has emerged as the central processing unit in many of these functions.
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spelling pubmed-87637782022-01-31 Molecular Basis of Coupled Transport and Anion Conduction in Excitatory Amino Acid Transporters Alleva, Claudia Machtens, Jan-Philipp Kortzak, Daniel Weyand, Ingo Fahlke, Christoph Neurochem Res Original Paper Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. After its release from presynaptic nerve terminals, glutamate is quickly removed from the synaptic cleft by excitatory amino acid transporters (EAATs) 1–5, a subfamily of glutamate transporters. The five proteins utilize a complex transport stoichiometry that couples glutamate transport to the symport of three Na(+) ions and one H(+) in exchange with one K(+) to accumulate glutamate against up to 10(6)-fold concentration gradients. They are also anion-selective channels that open and close during transitions along the glutamate transport cycle. EAATs belong to a larger family of secondary-active transporters, the SLC1 family, which also includes purely Na(+)- or H(+)-coupled prokaryotic transporters and Na(+)-dependent neutral amino acid exchangers. In recent years, molecular cloning, heterologous expression, cellular electrophysiology, fluorescence spectroscopy, structural approaches, and molecular simulations have uncovered the molecular mechanisms of coupled transport, substrate selectivity, and anion conduction in EAAT glutamate transporters. Here we review recent findings on EAAT transport mechanisms, with special emphasis on the highly conserved hairpin 2 gate, which has emerged as the central processing unit in many of these functions. Springer US 2021-02-15 2022 /pmc/articles/PMC8763778/ /pubmed/33587237 http://dx.doi.org/10.1007/s11064-021-03252-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Paper
Alleva, Claudia
Machtens, Jan-Philipp
Kortzak, Daniel
Weyand, Ingo
Fahlke, Christoph
Molecular Basis of Coupled Transport and Anion Conduction in Excitatory Amino Acid Transporters
title Molecular Basis of Coupled Transport and Anion Conduction in Excitatory Amino Acid Transporters
title_full Molecular Basis of Coupled Transport and Anion Conduction in Excitatory Amino Acid Transporters
title_fullStr Molecular Basis of Coupled Transport and Anion Conduction in Excitatory Amino Acid Transporters
title_full_unstemmed Molecular Basis of Coupled Transport and Anion Conduction in Excitatory Amino Acid Transporters
title_short Molecular Basis of Coupled Transport and Anion Conduction in Excitatory Amino Acid Transporters
title_sort molecular basis of coupled transport and anion conduction in excitatory amino acid transporters
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763778/
https://www.ncbi.nlm.nih.gov/pubmed/33587237
http://dx.doi.org/10.1007/s11064-021-03252-x
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