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Myosin V functions as a vesicle tether at the plasma membrane to control neurotransmitter release in central synapses

  1. Dario Maschi
  2. Michael Gramlich
  3. Vitaly Klyachko  Is a corresponding author
  1. Washington University, United States
Research Article
  • Cited 8
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Cite this article as: eLife 2018;7:e39440 doi: 10.7554/eLife.39440


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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Author details

  1. Dario Maschi

    Department of Cell Biology and Physiology, Washington University, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Michael Gramlich

    Department of Cell Biology and Physiology, Washington University, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Vitaly Klyachko

    Department of Cell Biology and Physiology, Washington University, St Louis, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3449-243X


National Institute of Neurological Disorders and Stroke (NS105776)

  • Vitaly Klyachko

CIMED Center at Washington University

  • Vitaly Klyachko

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.


Animal experimentation: All animal procedures were in compliance with the US National Institutes of Health Guide for the Care and Use of Laboratory Animals. All animal procedures conformed to the guidelines approved by the Washington University Animal Studies Committee (protocol approval # 20170233).

Reviewing Editor

  1. Yukiko Goda, RIKEN, Japan

Publication history

  1. Received: June 23, 2018
  2. Accepted: October 11, 2018
  3. Accepted Manuscript published: October 15, 2018 (version 1)
  4. Version of Record published: October 31, 2018 (version 2)


© 2018, Maschi et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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