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Syntaxins on granules promote docking of granules via interactions with munc18
SNAREs and SNARE-binding accessory proteins are believed to be central molecular components of neurotransmitter release, although the precise sequence of molecular events corresponding to distinct physiological states is unclear. The mechanism of docking of vesicles to the plasma membrane remains el...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760731/ https://www.ncbi.nlm.nih.gov/pubmed/29317735 http://dx.doi.org/10.1038/s41598-017-18597-z |
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author | Borisovska, Maria |
author_facet | Borisovska, Maria |
author_sort | Borisovska, Maria |
collection | PubMed |
description | SNAREs and SNARE-binding accessory proteins are believed to be central molecular components of neurotransmitter release, although the precise sequence of molecular events corresponding to distinct physiological states is unclear. The mechanism of docking of vesicles to the plasma membrane remains elusive, as the anchoring protein residing on vesicles is unknown. Here I show that targeting small amounts of syntaxin to granules by transmembrane domain alteration leads to a substantial enhancement of syntaxin clustering beneath granules, as well as of morphological granule docking. The effect was abolished without munc18 and strongly reduced by removal of the N-terminal peptide in the syntaxin mutant. Thus, in contrast to the current paradigm, I demonstrate that syntaxin acts from the vesicular membrane, strongly facilitating docking of vesicles, likely via interaction of its N-peptide with munc18. Docking was assayed by quantifying the syntaxin clusters beneath granules, using two-color Total Internal Reflectance Fluorescence microscopy in live PC-12 cells and confirmed by electron microscopy. Hereby, I propose a new model of vesicle docking, wherein munc18 bridges the few syntaxin molecules residing on granules to the syntaxin cluster on the plasma membrane, suggesting that the number of syntaxins on vesicles determines docking and conceivably fusion probability. |
format | Online Article Text |
id | pubmed-5760731 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57607312018-01-17 Syntaxins on granules promote docking of granules via interactions with munc18 Borisovska, Maria Sci Rep Article SNAREs and SNARE-binding accessory proteins are believed to be central molecular components of neurotransmitter release, although the precise sequence of molecular events corresponding to distinct physiological states is unclear. The mechanism of docking of vesicles to the plasma membrane remains elusive, as the anchoring protein residing on vesicles is unknown. Here I show that targeting small amounts of syntaxin to granules by transmembrane domain alteration leads to a substantial enhancement of syntaxin clustering beneath granules, as well as of morphological granule docking. The effect was abolished without munc18 and strongly reduced by removal of the N-terminal peptide in the syntaxin mutant. Thus, in contrast to the current paradigm, I demonstrate that syntaxin acts from the vesicular membrane, strongly facilitating docking of vesicles, likely via interaction of its N-peptide with munc18. Docking was assayed by quantifying the syntaxin clusters beneath granules, using two-color Total Internal Reflectance Fluorescence microscopy in live PC-12 cells and confirmed by electron microscopy. Hereby, I propose a new model of vesicle docking, wherein munc18 bridges the few syntaxin molecules residing on granules to the syntaxin cluster on the plasma membrane, suggesting that the number of syntaxins on vesicles determines docking and conceivably fusion probability. Nature Publishing Group UK 2018-01-09 /pmc/articles/PMC5760731/ /pubmed/29317735 http://dx.doi.org/10.1038/s41598-017-18597-z 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 Borisovska, Maria Syntaxins on granules promote docking of granules via interactions with munc18 |
title | Syntaxins on granules promote docking of granules via interactions with munc18 |
title_full | Syntaxins on granules promote docking of granules via interactions with munc18 |
title_fullStr | Syntaxins on granules promote docking of granules via interactions with munc18 |
title_full_unstemmed | Syntaxins on granules promote docking of granules via interactions with munc18 |
title_short | Syntaxins on granules promote docking of granules via interactions with munc18 |
title_sort | syntaxins on granules promote docking of granules via interactions with munc18 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760731/ https://www.ncbi.nlm.nih.gov/pubmed/29317735 http://dx.doi.org/10.1038/s41598-017-18597-z |
work_keys_str_mv | AT borisovskamaria syntaxinsongranulespromotedockingofgranulesviainteractionswithmunc18 |