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

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.

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)"

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

  • 2,815
    views
  • 366
    downloads
  • 18
    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

Further reading

    1. Cancer Biology
    2. Cell Biology
    Ida Marie Boisen, Nadia Krarup Knudsen ... Martin Blomberg Jensen
    Research Article

    Testicular microcalcifications consist of hydroxyapatite and have been associated with an increased risk of testicular germ cell tumors (TGCTs) but are also found in benign cases such as loss-of-function variants in the phosphate transporter SLC34A2. Here, we show that fibroblast growth factor 23 (FGF23), a regulator of phosphate homeostasis, is expressed in testicular germ cell neoplasia in situ (GCNIS), embryonal carcinoma (EC), and human embryonic stem cells. FGF23 is not glycosylated in TGCTs and therefore cleaved into a C-terminal fragment which competitively antagonizes full-length FGF23. Here, Fgf23 knockout mice presented with marked calcifications in the epididymis, spermatogenic arrest, and focally germ cells expressing the osteoblast marker Osteocalcin (gene name: Bglap, protein name). Moreover, the frequent testicular microcalcifications in mice with no functional androgen receptor and lack of circulating gonadotropins are associated with lower Slc34a2 and higher Bglap/Slc34a1 (protein name: NPT2a) expression compared with wild-type mice. In accordance, human testicular specimens with microcalcifications also have lower SLC34A2 and a subpopulation of germ cells express phosphate transporter NPT2a, Osteocalcin, and RUNX2 highlighting aberrant local phosphate handling and expression of bone-specific proteins. Mineral disturbance in vitro using calcium or phosphate treatment induced deposition of calcium phosphate in a spermatogonial cell line and this effect was fully rescued by the mineralization inhibitor pyrophosphate. In conclusion, testicular microcalcifications arise secondary to local alterations in mineral homeostasis, which in combination with impaired Sertoli cell function and reduced levels of mineralization inhibitors due to high alkaline phosphatase activity in GCNIS and TGCTs facilitate osteogenic-like differentiation of testicular cells and deposition of hydroxyapatite.

    1. Cell Biology
    Affiong Ika Oqua, Kin Chao ... Alejandra Tomas
    Research Article

    G protein-coupled receptors (GPCRs) are integral membrane proteins which closely interact with their plasma membrane lipid microenvironment. Cholesterol is a lipid enriched at the plasma membrane with pivotal roles in the control of membrane fluidity and maintenance of membrane microarchitecture, directly impacting on GPCR stability, dynamics, and function. Cholesterol extraction from pancreatic beta cells has previously been shown to disrupt the internalisation, clustering, and cAMP responses of the glucagon-like peptide-1 receptor (GLP-1R), a class B1 GPCR with key roles in the control of blood glucose levels via the potentiation of insulin secretion in beta cells and weight reduction via the modulation of brain appetite control centres. Here, we unveil the detrimental effect of a high cholesterol diet on GLP-1R-dependent glucoregulation in vivo, and the improvement in GLP-1R function that a reduction in cholesterol synthesis using simvastatin exerts in pancreatic islets. We next identify and map sites of cholesterol high occupancy and residence time on active vs inactive GLP-1Rs using coarse-grained molecular dynamics (cgMD) simulations, followed by a screen of key residues selected from these sites and detailed analyses of the effects of mutating one of these, Val229, to alanine on GLP-1R-cholesterol interactions, plasma membrane behaviours, clustering, trafficking and signalling in INS-1 832/3 rat pancreatic beta cells and primary mouse islets, unveiling an improved insulin secretion profile for the V229A mutant receptor. This study (1) highlights the role of cholesterol in regulating GLP-1R responses in vivo; (2) provides a detailed map of GLP-1R - cholesterol binding sites in model membranes; (3) validates their functional relevance in beta cells; and (4) highlights their potential as locations for the rational design of novel allosteric modulators with the capacity to fine-tune GLP-1R responses.