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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Main Authors: Dario Maschi, Michael W Gramlich, Vitaly A Klyachko
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2018-10-01
Series:eLife
Subjects:
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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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
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AT vitalyaklyachko myosinvfunctionsasavesicletetherattheplasmamembranetocontrolneurotransmitterreleaseincentralsynapses