1. Cell Biology
  2. Neuroscience

Photoreceptor disc incisures form as an adaptive mechanism ensuring the completion of disc enclosure

  1. Tylor R Lewis  Is a corresponding author
  2. Sebastien Phan
  3. Carson M Castillo
  4. Keun-Young Kim
  5. Kelsey Coppenrath
  6. William Thomas
  7. Ying Hao
  8. Nikolai P Skiba
  9. Marko E Horb
  10. Mark H Ellisman
  11. Vadim Y Arshavsky  Is a corresponding author
  1. Duke University, United States
  2. University of California, San Diego, United States
  3. Marine Biological Laboratory, United States
https://doi.org/10.7554/eLife.89160
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Cite this article
  1. Tylor R Lewis
  2. Sebastien Phan
  3. Carson M Castillo
  4. Keun-Young Kim
  5. Kelsey Coppenrath
  6. William Thomas
  7. Ying Hao
  8. Nikolai P Skiba
  9. Marko E Horb
  10. Mark H Ellisman
  11. Vadim Y Arshavsky
(2023)
Photoreceptor disc incisures form as an adaptive mechanism ensuring the completion of disc enclosure
eLife 12:e89160.
https://doi.org/10.7554/eLife.89160
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Abstract

The first steps of vision take place within a stack of tightly packed disc-shaped membranes, or 'discs', located in the outer segment compartment of photoreceptor cells. In rod photoreceptors, discs are enclosed inside the outer segment and contain deep indentations in their rims called 'incisures'. The presence of incisures has been documented in a variety of species, yet their role remains elusive. In this study, we combined traditional electron microscopy with three-dimensional electron tomography to demonstrate that incisures are formed only after discs become completely enclosed. We also observed that, at the earliest stage of their formation, discs are not round as typically depicted but rather are highly irregular in shape and resemble expanding lamellipodia. Using genetically manipulated mice and frogs and measuring outer segment protein abundances by quantitative mass spectrometry, we further found that incisure size is determined by the molar ratio between peripherin-2, a disc rim protein critical for the process of disc enclosure, and rhodopsin, the major structural component of disc membranes. While a high perpherin-2 to rhodopsin ratio causes an increase in incisure size and structural complexity, a low ratio precludes incisure formation. Based on these data, we propose a model whereby normal rods express a modest excess of peripherin-2 over the amount required for complete disc enclosure in order to ensure that this important step of disc formation is accomplished. Once the disc is enclosed, the excess peripherin-2 incorporates into the rim to form an incisure.

Data availability

All data generated or analyzed for this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Tylor R Lewis

    Department of Ophthalmology, Duke University, Durham, United States
    For correspondence
    tylor.lewis@duke.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6832-7972

  2. Sebastien Phan

    National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Carson M Castillo

    Department of Ophthalmology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Keun-Young Kim

    National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Kelsey Coppenrath

    Eugene Bell Center for Regenerative Biology and Tissue Engineering, Marine Biological Laboratory, Woods Hole, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. William Thomas

    Eugene Bell Center for Regenerative Biology and Tissue Engineering, Marine Biological Laboratory, Woods Hole, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Ying Hao

    Department of Ophthalmology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Nikolai P Skiba

    Department of Ophthalmology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Marko E Horb

    Eugene Bell Center for Regenerative Biology and Tissue Engineering, Marine Biological Laboratory, Woods Hole, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. Mark H Ellisman

    National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.

  11. Vadim Y Arshavsky

    Department of Ophthalmology, Duke University, Durham, United States
    For correspondence
    vadim.arshavsky@duke.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8394-3650

Funding

National Institutes of Health (EY030451)

  • Vadim Y Arshavsky

National Institutes of Health (EY005722)

  • Vadim Y Arshavsky

National Institutes of Health (EY033763)

  • Tylor R Lewis

National Institutes of Health (OD010997)

  • Marko E Horb

National Institutes of Health (OD030008)

  • Marko E Horb

Research to Prevent Blindness (Unrestricted Award)

  • Vadim Y Arshavsky

National Institutes of Health (NS120055)

  • Mark H Ellisman

National Institutes of Health (GM82949)

  • Mark H Ellisman

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

Ethics

Animal experimentation: Animal maintenance and experiments were approved by the Institutional Animal Care and Use Committees at Duke (Durham, NC; protocol #A184-22-10) and the Marine Biological Laboratory (Woods Hole, MA; protocol #22-29).

Copyright

© 2023, Lewis 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. Tylor R Lewis
  2. Sebastien Phan
  3. Carson M Castillo
  4. Keun-Young Kim
  5. Kelsey Coppenrath
  6. William Thomas
  7. Ying Hao
  8. Nikolai P Skiba
  9. Marko E Horb
  10. Mark H Ellisman
  11. Vadim Y Arshavsky
(2023)
Photoreceptor disc incisures form as an adaptive mechanism ensuring the completion of disc enclosure
eLife 12:e89160.
https://doi.org/10.7554/eLife.89160

Share this article

https://doi.org/10.7554/eLife.89160

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