1. Cell Biology
  2. Physics of Living Systems

Rod nuclear architecture determines contrast transmission of the retina and behavioral sensitivity in mice

  1. Kaushikaram Subramanian
  2. Martin Weigert
  3. Oliver Borsch
  4. Heike Petzold
  5. Alfonso Garcia-Ulloa
  6. Eugene W Myers
  7. Marius Ader
  8. Irina Solovei
  9. Moritz Kreysing  Is a corresponding author
  1. Max Planck Institute of Molecular Cell Biology and Genetics, Germany
  2. Technische Universität Dresden, Germany
  3. Ludwig Maximilians Universität, Germany
https://doi.org/10.7554/eLife.49542
Share this article
Cite this article
  1. Kaushikaram Subramanian
  2. Martin Weigert
  3. Oliver Borsch
  4. Heike Petzold
  5. Alfonso Garcia-Ulloa
  6. Eugene W Myers
  7. Marius Ader
  8. Irina Solovei
  9. Moritz Kreysing
(2019)
Rod nuclear architecture determines contrast transmission of the retina and behavioral sensitivity in mice
eLife 8:e49542.
https://doi.org/10.7554/eLife.49542
  2. Download BibTeX
  3. Download .RIS

Abstract

Rod photoreceptors of nocturnal mammals display a striking inversion of nuclear architecture, which has been proposed as an evolutionary adaptation to dark environments. However, the nature of visual benefits and the underlying mechanisms remains unclear. It is widely assumed that improvements in nocturnal vision would depend on maximization of photon capture at the expense of image detail. Here we show that retinal optical quality improves 2-fold during terminal development, and that this enhancement is caused by nuclear inversion. We further demonstrate that improved retinal contrast transmission, rather than photon-budget or resolution, enhances scotopic contrast sensitivity by 18-27%, and improves motion detection capabilities up to 10-fold in dim environments. Our findings therefore add functional significance to a prominent exception of nuclear organization and establish retinal contrast transmission as a decisive determinant of mammalian visual perception.

Data availability

Data and specifications of simulations supporting the findings of this study are available via https://owncloud.mpi-cbg.de/index.php/s/SaCJjsMCfyOAaTb . The biobeam software is available publicly from: https://maweigert.github.io/biobeam

Article and author information

Author details

  1. Kaushikaram Subramanian

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.

  2. Martin Weigert

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.

  3. Oliver Borsch

    Center for Regenerative Therapies, Technische Universität Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.

  4. Heike Petzold

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.

  5. Alfonso Garcia-Ulloa

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.

  6. Eugene W Myers

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.

  7. Marius Ader

    Center for Regenerative Therapies, Technische Universität Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9467-7677

  8. Irina Solovei

    Biozentrum, Ludwig Maximilians Universität, München, Germany
    Competing interests
    The authors declare that no competing interests exist.

  9. Moritz Kreysing

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    For correspondence
    kreysing@mpi-cbg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7432-3871

Funding

Max-Planck-Gesellschaft

  • Kaushikaram Subramanian
  • Martin Weigert
  • Heike Petzold
  • Alfonso Garcia-Ulloa
  • Eugene W Myers
  • Moritz Kreysing

Technische Universität Dresden

  • Oliver Borsch
  • Marius Ader

Deutsche Forschungsgemeinschaft (AD375/6-1)

  • Oliver Borsch
  • Marius Ader

Bundesministerium für Bildung und Forschung (031L0044)

  • Kaushikaram Subramanian
  • Eugene W Myers
  • Moritz Kreysing

Deutsche Forschungsgemeinschaft (SO1054/3)

  • Irina Solovei

Deutsche Forschungsgemeinschaft (FZT111)

  • Oliver Borsch
  • Marius Ader

Deutsche Forschungsgemeinschaft (EXC68)

  • Oliver Borsch
  • Marius Ader

Deutsche Forschungsgemeinschaft (SFB1064)

  • Irina Solovei

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

Reviewing Editor

  1. Jeremy Nathans, Johns Hopkins University School of Medicine, United States

Ethics

Animal experimentation: "All animal studies were performed in accordance with European and German animal welfare legislation (Tierschutzgesetz), the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research, and the NIH Guide for the care and use of laboratory work in strict pathogen-free conditions in the animal facilities of the Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany and the Center for Regenerative Therapies Dresden, Germany. Protocols were approved by the Institutional Animal Welfare Officer (Tierschutzbeauftragter) and the ethics committee of the TU Dresden. Necessary licenses 24-9168.24-9/2012-1, DD24.1-5131/451/8 and TVV 16/2018 (DD24-5131/354/19) were obtained from the regional Ethical Commission for Animal Experimentation of Dresden, Germany (Tierversuchskommission, Landesdirektion Sachsen)"

Version history

  1. Received: June 20, 2019
  2. Accepted: December 11, 2019
  3. Accepted Manuscript published: December 11, 2019 (version 1)
  4. Version of Record published: January 21, 2020 (version 2)

Copyright

© 2019, Subramanian 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

  • 2,607
    views
  • 342
    downloads
  • 15
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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)

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

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

  1. Kaushikaram Subramanian
  2. Martin Weigert
  3. Oliver Borsch
  4. Heike Petzold
  5. Alfonso Garcia-Ulloa
  6. Eugene W Myers
  7. Marius Ader
  8. Irina Solovei
  9. Moritz Kreysing
(2019)
Rod nuclear architecture determines contrast transmission of the retina and behavioral sensitivity in mice
eLife 8:e49542.
https://doi.org/10.7554/eLife.49542

Share this article

https://doi.org/10.7554/eLife.49542

Categories and tags

Research organism

Further reading

    1. Cell Biology
    2. Neuroscience

    Unraveling the link between neuropathy target esterase NTE/SWS, lysosomal storage diseases, inflammation, abnormal fatty acid metabolism, and leaky brain barrier

    Mariana I Tsap, Andriy S Yatsenko ... Halyna R Shcherbata
    Research Article Updated

    Mutations in Drosophila Swiss cheese (SWS) gene or its vertebrate orthologue neuropathy target esterase (NTE) lead to progressive neuronal degeneration in flies and humans. Despite its enzymatic function as a phospholipase is well established, the molecular mechanism responsible for maintaining nervous system integrity remains unclear. In this study, we found that NTE/SWS is present in surface glia that forms the blood-brain barrier (BBB) and that NTE/SWS is important to maintain its structure and permeability. Importantly, BBB glia-specific expression of Drosophila NTE/SWS or human NTE in the sws mutant background fully rescues surface glial organization and partially restores BBB integrity, suggesting a conserved function of NTE/SWS. Interestingly, sws mutant glia showed abnormal organization of plasma membrane domains and tight junction rafts accompanied by the accumulation of lipid droplets, lysosomes, and multilamellar bodies. Since the observed cellular phenotypes closely resemble the characteristics described in a group of metabolic disorders known as lysosomal storage diseases (LSDs), our data established a novel connection between NTE/SWS and these conditions. We found that mutants with defective BBB exhibit elevated levels of fatty acids, which are precursors of eicosanoids and are involved in the inflammatory response. Also, as a consequence of a permeable BBB, several innate immunity factors are upregulated in an age-dependent manner, while BBB glia-specific expression of NTE/SWS normalizes inflammatory response. Treatment with anti-inflammatory agents prevents the abnormal architecture of the BBB, suggesting that inflammation contributes to the maintenance of a healthy brain barrier. Considering the link between a malfunctioning BBB and various neurodegenerative diseases, gaining a deeper understanding of the molecular mechanisms causing inflammation due to a defective BBB could help to promote the use of anti-inflammatory therapies for age-related neurodegeneration.

    1. Cancer Biology
    2. Cell Biology

    mTORC1/S6K1 signaling promotes sustained oncogenic translation through modulating CRL3IBTK-mediated ubiquitination of eIF4A1 in cancer cells

    Dongyue Jiao, Huiru Sun ... Kun Gao
    Research Article

    Enhanced protein synthesis is a crucial molecular mechanism that allows cancer cells to survive, proliferate, metastasize, and develop resistance to anti-cancer treatments, and often arises as a consequence of increased signaling flux channeled to mRNA-bearing eukaryotic initiation factor 4F (eIF4F). However, the post-translational regulation of eIF4A1, an ATP-dependent RNA helicase and subunit of the eIF4F complex, is still poorly understood. Here, we demonstrate that IBTK, a substrate-binding adaptor of the Cullin 3-RING ubiquitin ligase (CRL3) complex, interacts with eIF4A1. The non-degradative ubiquitination of eIF4A1 catalyzed by the CRL3IBTK complex promotes cap-dependent translational initiation, nascent protein synthesis, oncogene expression, and cervical tumor cell growth both in vivo and in vitro. Moreover, we show that mTORC1 and S6K1, two key regulators of protein synthesis, directly phosphorylate IBTK to augment eIF4A1 ubiquitination and sustained oncogenic translation. This link between the CRL3IBTK complex and the mTORC1/S6K1 signaling pathway, which is frequently dysregulated in cancer, represents a promising target for anti-cancer therapies.

    1. Biochemistry and Chemical Biology
    2. Cell Biology

    MEMO1 binds iron and modulates iron homeostasis in cancer cells

    Natalia Dolgova, Eva-Maria E Uhlemann ... Oleg Y Dmitriev
    Research Article Updated

    Mediator of ERBB2-driven cell motility 1 (MEMO1) is an evolutionary conserved protein implicated in many biological processes; however, its primary molecular function remains unknown. Importantly, MEMO1 is overexpressed in many types of cancer and was shown to modulate breast cancer metastasis through altered cell motility. To better understand the function of MEMO1 in cancer cells, we analyzed genetic interactions of MEMO1 using gene essentiality data from 1028 cancer cell lines and found multiple iron-related genes exhibiting genetic relationships with MEMO1. We experimentally confirmed several interactions between MEMO1 and iron-related proteins in living cells, most notably, transferrin receptor 2 (TFR2), mitoferrin-2 (SLC25A28), and the global iron response regulator IRP1 (ACO1). These interactions indicate that cells with high-MEMO1 expression levels are hypersensitive to the disruptions in iron distribution. Our data also indicate that MEMO1 is involved in ferroptosis and is linked to iron supply to mitochondria. We have found that purified MEMO1 binds iron with high affinity under redox conditions mimicking intracellular environment and solved MEMO1 structures in complex with iron and copper. Our work reveals that the iron coordination mode in MEMO1 is very similar to that of iron-containing extradiol dioxygenases, which also display a similar structural fold. We conclude that MEMO1 is an iron-binding protein that modulates iron homeostasis in cancer cells.