1. Neuroscience
Download icon

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 4
  • Views 1,747
  • Annotations
Cite this article as: eLife 2018;7:e39440 doi: 10.7554/eLife.39440

Abstract

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.

Article and author information

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
    klyachko@wustl.edu
    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

Funding

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.

Ethics

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)

Copyright

© 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.

Metrics

  • 1,747
    Page views
  • 388
    Downloads
  • 4
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Neuroscience
    Cristina Blázquez et al.
    Research Article

    The use of cannabis is rapidly expanding worldwide. Thus, innovative studies aimed to identify, understand and potentially reduce cannabis-evoked harms are warranted. Here, we found that Δ9-tetrahydrocannabinol, the psychoactive ingredient of cannabis, disrupts autophagy selectively in the striatum, a brain area that controls motor behavior, both in vitro and in vivo. Boosting autophagy, either pharmacologically (with temsirolimus) or by dietary intervention (with trehalose), rescued the Δ9-tetrahydrocannabinol-induced impairment of motor coordination in mice. The combination of conditional knockout mouse models and viral vector-mediated autophagy-modulating strategies in vivo showed that cannabinoid CB1 receptors located on neurons belonging to the direct (striatonigral) pathway are required for the motor-impairing activity of Δ9-tetrahydrocannabinol by inhibiting local autophagy. Taken together, these findings identify inhibition of autophagy as an unprecedented mechanistic link between cannabinoids and motor performance, and suggest that activators of autophagy might be considered as potential therapeutic tools to treat specific cannabinoid-evoked behavioral alterations.

    1. Developmental Biology
    2. Neuroscience
    Konstantinos Lagogiannis et al.
    Research Article

    Goal-directed behaviours may be poorly coordinated in young animals but, with age and experience, behaviour progressively adapts to efficiently exploit the animal's ecological niche. How experience impinges on the developing neural circuits of behaviour is an open question. We have conducted a detailed study of the effects of experience on the ontogeny of hunting behaviour in larval zebrafish. We report that larvae with prior experience of live prey consume considerably more prey than naive larvae. This is mainly due to increased capture success and a modest increase in hunt rate. We demonstrate that the initial turn to prey and the final capture manoeuvre of the hunting sequence were jointly modified by experience and that modification of these components predicted capture success. Our findings establish an ethologically relevant paradigm in zebrafish for studying how the brain is shaped by experience to drive the ontogeny of efficient behaviour.