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Microtubule depolymerization contributes to spontaneous neurotransmitter release in vitro
Microtubules are key to multiple neuronal functions involving the transport of organelles, however, their relationship to neurotransmitter release is still unresolved. Here, we show that microtubules present in the presynaptic compartment of cholinergic autaptic synapses are dynamic. To investigate...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10163034/ https://www.ncbi.nlm.nih.gov/pubmed/37147475 http://dx.doi.org/10.1038/s42003-023-04779-1 |
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author | Velasco, Cecilia D. Santarella-Mellwig, Rachel Schorb, Martin Gao, Li Thorn-Seshold, Oliver Llobet, Artur |
author_facet | Velasco, Cecilia D. Santarella-Mellwig, Rachel Schorb, Martin Gao, Li Thorn-Seshold, Oliver Llobet, Artur |
author_sort | Velasco, Cecilia D. |
collection | PubMed |
description | Microtubules are key to multiple neuronal functions involving the transport of organelles, however, their relationship to neurotransmitter release is still unresolved. Here, we show that microtubules present in the presynaptic compartment of cholinergic autaptic synapses are dynamic. To investigate how the balance between microtubule growth and shrinkage affects neurotransmission we induced synchronous microtubule depolymerization by photoactivation of the chemical inhibitor SBTub3. The consequence was an increase in spontaneous neurotransmitter release. An analogous effect was obtained by dialyzing the cytosol with Kif18A, a plus-end-directed kinesin with microtubule depolymerizing activity. Kif18A also inhibited the refilling of the readily releasable pool of synaptic vesicles during high frequency stimulation. The action of Kif18A was associated to one order of magnitude increases in the numbers of exo-endocytic pits and endosomes present in the presynaptic terminal. An enhancement of spontaneous neurotransmitter release was also observed when neurons were dialyzed with stathmin-1, a protein with a widespread presence in the nervous system that induces microtubule depolymerization. Taken together, these results support that microtubules restrict spontaneous neurotransmitter release as well as promote the replenishment of the readily releasable pool of synaptic vesicles. |
format | Online Article Text |
id | pubmed-10163034 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-101630342023-05-07 Microtubule depolymerization contributes to spontaneous neurotransmitter release in vitro Velasco, Cecilia D. Santarella-Mellwig, Rachel Schorb, Martin Gao, Li Thorn-Seshold, Oliver Llobet, Artur Commun Biol Article Microtubules are key to multiple neuronal functions involving the transport of organelles, however, their relationship to neurotransmitter release is still unresolved. Here, we show that microtubules present in the presynaptic compartment of cholinergic autaptic synapses are dynamic. To investigate how the balance between microtubule growth and shrinkage affects neurotransmission we induced synchronous microtubule depolymerization by photoactivation of the chemical inhibitor SBTub3. The consequence was an increase in spontaneous neurotransmitter release. An analogous effect was obtained by dialyzing the cytosol with Kif18A, a plus-end-directed kinesin with microtubule depolymerizing activity. Kif18A also inhibited the refilling of the readily releasable pool of synaptic vesicles during high frequency stimulation. The action of Kif18A was associated to one order of magnitude increases in the numbers of exo-endocytic pits and endosomes present in the presynaptic terminal. An enhancement of spontaneous neurotransmitter release was also observed when neurons were dialyzed with stathmin-1, a protein with a widespread presence in the nervous system that induces microtubule depolymerization. Taken together, these results support that microtubules restrict spontaneous neurotransmitter release as well as promote the replenishment of the readily releasable pool of synaptic vesicles. Nature Publishing Group UK 2023-05-05 /pmc/articles/PMC10163034/ /pubmed/37147475 http://dx.doi.org/10.1038/s42003-023-04779-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Velasco, Cecilia D. Santarella-Mellwig, Rachel Schorb, Martin Gao, Li Thorn-Seshold, Oliver Llobet, Artur Microtubule depolymerization contributes to spontaneous neurotransmitter release in vitro |
title | Microtubule depolymerization contributes to spontaneous neurotransmitter release in vitro |
title_full | Microtubule depolymerization contributes to spontaneous neurotransmitter release in vitro |
title_fullStr | Microtubule depolymerization contributes to spontaneous neurotransmitter release in vitro |
title_full_unstemmed | Microtubule depolymerization contributes to spontaneous neurotransmitter release in vitro |
title_short | Microtubule depolymerization contributes to spontaneous neurotransmitter release in vitro |
title_sort | microtubule depolymerization contributes to spontaneous neurotransmitter release in vitro |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10163034/ https://www.ncbi.nlm.nih.gov/pubmed/37147475 http://dx.doi.org/10.1038/s42003-023-04779-1 |
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