Myosin V functions as a vesicle tether at the plasma membrane to control neurotransmitter release in central synapses
Synaptic vesicle fusion occurs at specialized release sites at the active zone. How refilling of release sites with new vesicles is regulated in central synapses remains poorly understood. Using nanoscale-resolution detection of individual release events in rat hippocampal synapses we found that inh...
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Format: | Article |
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eLife Sciences Publications Ltd
2018-10-01
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Series: | eLife |
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Online Access: | https://elifesciences.org/articles/39440 |
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author | Dario Maschi Michael W Gramlich Vitaly A Klyachko |
author_facet | Dario Maschi Michael W Gramlich Vitaly A Klyachko |
author_sort | Dario Maschi |
collection | DOAJ |
description | Synaptic vesicle fusion occurs at specialized release sites at the active zone. How refilling of release sites with new vesicles is regulated in central synapses remains poorly understood. Using nanoscale-resolution detection of individual release events in rat hippocampal synapses we found that inhibition of myosin V, the predominant vesicle-associated motor, strongly reduced refilling of the release sites during repetitive stimulation. Single-vesicle tracking revealed that recycling vesicles continuously shuttle between a plasma membrane pool and an inner pool. Vesicle retention at the membrane pool was regulated by neural activity in a myosin V dependent manner. Ultrastructural measurements of vesicle occupancy at the plasma membrane together with analyses of single-vesicle trajectories during vesicle shuttling between the pools suggest that myosin V acts as a vesicle tether at the plasma membrane, rather than a motor transporting vesicles to the release sites, or directly regulating vesicle exocytosis. |
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format | Article |
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institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-04-12T16:44:10Z |
publishDate | 2018-10-01 |
publisher | eLife Sciences Publications Ltd |
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spelling | doaj.art-53dd6f876586402ea439b13dc27767a62022-12-22T03:24:39ZengeLife Sciences Publications LtdeLife2050-084X2018-10-01710.7554/eLife.39440Myosin V functions as a vesicle tether at the plasma membrane to control neurotransmitter release in central synapsesDario Maschi0Michael W Gramlich1Vitaly A Klyachko2https://orcid.org/0000-0003-3449-243XDepartment of Cell Biology and Physiology, Washington University, Missouri, United States; Department of Biomedical Engineering, Washington University, Missouri, United StatesDepartment of Cell Biology and Physiology, Washington University, Missouri, United States; Department of Biomedical Engineering, Washington University, Missouri, United StatesDepartment of Cell Biology and Physiology, Washington University, Missouri, United States; Department of Biomedical Engineering, Washington University, Missouri, United StatesSynaptic vesicle fusion occurs at specialized release sites at the active zone. How refilling of release sites with new vesicles is regulated in central synapses remains poorly understood. Using nanoscale-resolution detection of individual release events in rat hippocampal synapses we found that inhibition of myosin V, the predominant vesicle-associated motor, strongly reduced refilling of the release sites during repetitive stimulation. Single-vesicle tracking revealed that recycling vesicles continuously shuttle between a plasma membrane pool and an inner pool. Vesicle retention at the membrane pool was regulated by neural activity in a myosin V dependent manner. Ultrastructural measurements of vesicle occupancy at the plasma membrane together with analyses of single-vesicle trajectories during vesicle shuttling between the pools suggest that myosin V acts as a vesicle tether at the plasma membrane, rather than a motor transporting vesicles to the release sites, or directly regulating vesicle exocytosis.https://elifesciences.org/articles/39440neurotransmitter releasesynaptic vesiclerelease sitesingle-vesicle imagingmyosin Vactive zone |
spellingShingle | Dario Maschi Michael W Gramlich Vitaly A Klyachko Myosin V functions as a vesicle tether at the plasma membrane to control neurotransmitter release in central synapses eLife neurotransmitter release synaptic vesicle release site single-vesicle imaging myosin V active zone |
title | Myosin V functions as a vesicle tether at the plasma membrane to control neurotransmitter release in central synapses |
title_full | Myosin V functions as a vesicle tether at the plasma membrane to control neurotransmitter release in central synapses |
title_fullStr | Myosin V functions as a vesicle tether at the plasma membrane to control neurotransmitter release in central synapses |
title_full_unstemmed | Myosin V functions as a vesicle tether at the plasma membrane to control neurotransmitter release in central synapses |
title_short | Myosin V functions as a vesicle tether at the plasma membrane to control neurotransmitter release in central synapses |
title_sort | myosin v functions as a vesicle tether at the plasma membrane to control neurotransmitter release in central synapses |
topic | neurotransmitter release synaptic vesicle release site single-vesicle imaging myosin V active zone |
url | https://elifesciences.org/articles/39440 |
work_keys_str_mv | AT dariomaschi myosinvfunctionsasavesicletetherattheplasmamembranetocontrolneurotransmitterreleaseincentralsynapses AT michaelwgramlich myosinvfunctionsasavesicletetherattheplasmamembranetocontrolneurotransmitterreleaseincentralsynapses AT vitalyaklyachko myosinvfunctionsasavesicletetherattheplasmamembranetocontrolneurotransmitterreleaseincentralsynapses |