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The ins and outs of vesicular monoamine transporters
The H(+)-coupled vesicular monoamine transporter (VMAT) is a transporter essential for life. VMAT mediates packaging of the monoamines serotonin, dopamine, norepinephrine, and histamine from the neuronal cytoplasm into presynaptic vesicles, which is a key step in the regulated release of neurotransm...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940252/ https://www.ncbi.nlm.nih.gov/pubmed/29666153 http://dx.doi.org/10.1085/jgp.201711980 |
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author | Yaffe, Dana Forrest, Lucy R. Schuldiner, Shimon |
author_facet | Yaffe, Dana Forrest, Lucy R. Schuldiner, Shimon |
author_sort | Yaffe, Dana |
collection | PubMed |
description | The H(+)-coupled vesicular monoamine transporter (VMAT) is a transporter essential for life. VMAT mediates packaging of the monoamines serotonin, dopamine, norepinephrine, and histamine from the neuronal cytoplasm into presynaptic vesicles, which is a key step in the regulated release of neurotransmitters. However, a detailed understanding of the mechanism of VMAT function has been limited by the lack of availability of high-resolution structural data. In recent years, a series of studies guided by homology models has revealed significant insights into VMAT function, identifying residues that contribute to the binding site and to specific steps in the transport cycle. Moreover, to characterize the conformational transitions that occur upon binding of the substrate and coupling ion, we have taken advantage of the unique and powerful pharmacology of VMAT as well as of mutants that affect the conformational equilibrium of the protein and shift it toward defined conformations. This has allowed us to identify an important role for the proton gradient in driving a shift from lumen-facing to cytoplasm-facing conformations. |
format | Online Article Text |
id | pubmed-5940252 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-59402522018-11-07 The ins and outs of vesicular monoamine transporters Yaffe, Dana Forrest, Lucy R. Schuldiner, Shimon J Gen Physiol Reviews The H(+)-coupled vesicular monoamine transporter (VMAT) is a transporter essential for life. VMAT mediates packaging of the monoamines serotonin, dopamine, norepinephrine, and histamine from the neuronal cytoplasm into presynaptic vesicles, which is a key step in the regulated release of neurotransmitters. However, a detailed understanding of the mechanism of VMAT function has been limited by the lack of availability of high-resolution structural data. In recent years, a series of studies guided by homology models has revealed significant insights into VMAT function, identifying residues that contribute to the binding site and to specific steps in the transport cycle. Moreover, to characterize the conformational transitions that occur upon binding of the substrate and coupling ion, we have taken advantage of the unique and powerful pharmacology of VMAT as well as of mutants that affect the conformational equilibrium of the protein and shift it toward defined conformations. This has allowed us to identify an important role for the proton gradient in driving a shift from lumen-facing to cytoplasm-facing conformations. Rockefeller University Press 2018-05-07 /pmc/articles/PMC5940252/ /pubmed/29666153 http://dx.doi.org/10.1085/jgp.201711980 Text en © 2018 Yaffe et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Reviews Yaffe, Dana Forrest, Lucy R. Schuldiner, Shimon The ins and outs of vesicular monoamine transporters |
title | The ins and outs of vesicular monoamine transporters |
title_full | The ins and outs of vesicular monoamine transporters |
title_fullStr | The ins and outs of vesicular monoamine transporters |
title_full_unstemmed | The ins and outs of vesicular monoamine transporters |
title_short | The ins and outs of vesicular monoamine transporters |
title_sort | ins and outs of vesicular monoamine transporters |
topic | Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940252/ https://www.ncbi.nlm.nih.gov/pubmed/29666153 http://dx.doi.org/10.1085/jgp.201711980 |
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