IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms8006.html
   My bibliography  Save this article

Prdx4 is a compartment-specific H2O2 sensor that regulates neurogenesis by controlling surface expression of GDE2

Author

Listed:
  • Ye Yan

    (The Johns Hopkins University School of Medicine)

  • Cynthia Wladyka

    (The Johns Hopkins University School of Medicine)

  • Junichi Fujii

    (Yamagata University)

  • Shanthini Sockanathan

    (The Johns Hopkins University School of Medicine)

Abstract

Neural progenitors and terminally differentiated neurons show distinct redox profiles, suggesting that coupled-redox cascades regulate the initiation and progression of neuronal differentiation. Discrete cellular compartments have different redox environments and how they contribute to differentiation is unclear. Here we show that Prdx4, an endoplasmic reticulum (ER) enzyme that metabolizes H2O2, acts as a tunable regulator of neurogenesis via its compartmentalized thiol-oxidative function. Prdx4 ablation causes premature motor neuron differentiation and progenitor depletion, leading to imbalances in subtype-specific motor neurons. GDE2, a six-transmembrane protein that induces differentiation by downregulating Notch signalling through surface cleavage of GPI-anchored proteins, is targeted by Prdx4 oxidative activity. Prdx4 dimers generated by H2O2 metabolism oxidize two cysteine residues within the GDE2 enzymatic domain, which blocks GDE2 trafficking to the plasma membrane and prevents GDE2 neurogeneic function. Thus, Prdx4 oxidative activity acts as a sensor to directly couple neuronal differentiation with redox environments in the ER.

Suggested Citation

  • Ye Yan & Cynthia Wladyka & Junichi Fujii & Shanthini Sockanathan, 2015. "Prdx4 is a compartment-specific H2O2 sensor that regulates neurogenesis by controlling surface expression of GDE2," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8006
    DOI: 10.1038/ncomms8006
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms8006
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms8006?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Bernardo Gindri dos Santos & Caroline Peres Klein & Mariana Scortegagna Crestani & Rafael Moura Maurmann & Régis Mateus Hözer & Karoline dos Santos Rodrigues & Pauline Maciel August & Cristiane Matté, 2021. "Naringin Supplementation during Pregnancy Induces Sex and Region-Specific Alterations in the Offspring’s Brain Redox Status," IJERPH, MDPI, vol. 18(9), pages 1-20, April.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8006. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.