1. Neuroscience
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A dual role for Cav1.4 Ca2+ channels in the molecular and structural organization of the rod photoreceptor synapse

  1. J Wesley Maddox
  2. Kate L Randall
  3. Ravi P Yadav
  4. Brittany Williams
  5. Jussara Hagen
  6. Paul J Derr
  7. Vasily Kerov
  8. Luca Della Santina
  9. Sheila A Baker
  10. Nikolai Artemyev
  11. Mrinalini Hoon
  12. Amy Lee  Is a corresponding author
  1. University of Iowa, United States
  2. University of Wisconsin, Madison, United States
  3. University of California, San Francisco, United States
  4. University of Iowa Carver College of Medicine, United States
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Cite this article as: eLife 2020;9:e62184 doi: 10.7554/eLife.62184

Abstract

Synapses are fundamental information processing units that rely on voltage-gated Ca2+ (Cav) channels to trigger Ca2+-dependent neurotransmitter release. Cav channels also play Ca2+-independent roles in other biological contexts, but whether they do so in axon terminals is unknown. Here, we addressed this unknown with respect to the requirement for Cav1.4 L-type channels for the formation of rod photoreceptor synapses in the retina. Using a mouse strain expressing a non-conducting mutant form of Cav1.4, we report that the Cav1.4 protein, but not its Ca2+ conductance, is required for the molecular assembly of rod synapses; however, Cav1.4 Ca2+ signals are needed for the appropriate recruitment of postsynaptic partners. Our results support a model in which presynaptic Cav channels serve both as organizers of synaptic building blocks and as sources of Ca2+ ions in building the first synapse of the visual pathway and perhaps more broadly in the nervous system.

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All data generated or analysed during this study are included in the manuscript and supporting files

Article and author information

Author details

  1. J Wesley Maddox

    Molecular Physiology and Biophysics, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Kate L Randall

    Molecular Physiology and Biophysics, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ravi P Yadav

    Molecular Physiology and Biophysics, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Brittany Williams

    Molecular Physiology and Biophysics, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jussara Hagen

    Molecular Physiology and Biophysics, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Paul J Derr

    Neuroscience, University of Wisconsin, Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Vasily Kerov

    Molecular Physiology and Biophysics, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Luca Della Santina

    Department of Ophthalmology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Sheila A Baker

    Biochemistry, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Nikolai Artemyev

    Molecular Physiology, University of Iowa Carver College of Medicine, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Mrinalini Hoon

    Department of Neuroscience, University of Wisconsin, Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Amy Lee

    Molecular Physiology and Biophysics, University of Iowa, Iowa City, United States
    For correspondence
    amy-lee@uiowa.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8021-0443

Funding

National Eye Institute (EY 026817)

  • Amy Lee

McPherson Eye Research Institute

  • Mrinalini Hoon

Research to Prevent Blindness

  • Mrinalini Hoon

National Eye Institute (EY 029953)

  • J Wesley Maddox

National Eye Institute (EY 026477)

  • Brittany Williams

National Eye Institute (EY010843,EY012682)

  • Nikolai Artemyev

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#7121262-025) of the University of Iowa. The protocol was approved by the Office of Institutional Animal Care and Use Committee of the University of Iowa (A3021-01).

Reviewing Editor

  1. Teresa Giraldez, Universidad de La Laguna, Spain

Publication history

  1. Received: August 17, 2020
  2. Accepted: September 9, 2020
  3. Accepted Manuscript published: September 17, 2020 (version 1)
  4. Version of Record published: October 15, 2020 (version 2)

Copyright

© 2020, Maddox 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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