Abstract

To encode light-dependent changes in membrane potential, rod and cone photoreceptors utilize synaptic ribbons to sustain continuous exocytosis while making rapid, fine adjustments to release rate. Release kinetics are shaped by vesicle delivery down ribbons and by properties of exocytotic Ca2+ sensors. We tested the role for synaptotagmin-1 (Syt1) in photoreceptor exocytosis by using novel mouse lines in which Syt1 was conditionally removed from rods or cones. Photoreceptors lacking Syt1 exhibited marked reductions in exocytosis as measured by electroretinography and single-cell recordings. Syt1 mediated all evoked release in cones, whereas rods appeared capable of some slow Syt1-independent release. Spontaneous release frequency was unchanged in cones but increased in rods lacking Syt1. Loss of Syt1 did not alter synaptic anatomy or reduce Ca2+ currents. These results suggest that Syt1 mediates both phasic and tonic release at photoreceptor synapses, revealing unexpected flexibility in the ability of Syt1 to regulate Ca2+-dependent synaptic transmission.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figure 9.

Article and author information

Author details

  1. Justin J Grassmeyer

    Truhlsen Eye Institute, Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9624-9027
  2. Asia L Cahill

    Truhlsen Eye Institute, Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Cassandra L Hays

    Truhlsen Eye Institute, Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Cody Barta

    Truhlsen Eye Institute, Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Rolen M Quadros

    Mouse Genome Engineering Core Facility, Vice Chancellor for Research Office, University of Nebraska Medical Center, Omaha, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9798-9622
  6. Channabasavaiah B Gurumurthy

    Mouse Genome Engineering Core Facility, Vice Chancellor for Research Office, University of Nebraska Medical Center, Omaha, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8022-4033
  7. Wallace B Thoreson

    Truhlsen Eye Institute, Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, United States
    For correspondence
    wbthores@unmc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7104-042X

Funding

National Eye Institute (EY10542)

  • Wallace B Thoreson

Research to Prevent Blindness (Senior Scientific Investigator)

  • Wallace B Thoreson

National Eye Institute (EY28848)

  • Justin J Grassmeyer

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 care and handling protocols were approved by the University of Nebraska Medical Center Institutional Animal Care and Use Committee (protocols 15-027-00 and 15-028-04).

Reviewing Editor

  1. Reinhard Jahn, Max Planck Institute for Biophysical Chemistry, Germany

Version history

  1. Received: February 9, 2019
  2. Accepted: June 6, 2019
  3. Accepted Manuscript published: June 7, 2019 (version 1)
  4. Version of Record published: June 21, 2019 (version 2)

Copyright

© 2019, Grassmeyer 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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  1. Justin J Grassmeyer
  2. Asia L Cahill
  3. Cassandra L Hays
  4. Cody Barta
  5. Rolen M Quadros
  6. Channabasavaiah B Gurumurthy
  7. Wallace B Thoreson
(2019)
Ca2+ sensor synaptotagmin-1 mediates exocytosis in mammalian photoreceptors
eLife 8:e45946.
https://doi.org/10.7554/eLife.45946

Share this article

https://doi.org/10.7554/eLife.45946

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