IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms10118.html
   My bibliography  Save this article

Interneuronal DISC1 regulates NRG1-ErbB4 signalling and excitatory–inhibitory synapse formation in the mature cortex

Author

Listed:
  • Saurav Seshadri

    (Johns Hopkins University
    Present address: Section on Critical Brain Dynamics, National Institute of Mental Health, Bethesda, Maryland 20892, USA.)

  • Travis Faust

    (Johns Hopkins University)

  • Koko Ishizuka

    (Johns Hopkins University)

  • Kristen Delevich

    (Watson School of Biological Sciences, Cold Spring Harbor Laboratory)

  • Youjin Chung

    (Johns Hopkins University)

  • Sun-Hong Kim

    (Johns Hopkins University)

  • Martis Cowles

    (University of North Carolina)

  • Minae Niwa

    (Johns Hopkins University)

  • Hanna Jaaro-Peled

    (Johns Hopkins University)

  • Toshifumi Tomoda

    (Beckman Research Institute of City of Hope)

  • Cary Lai

    (Indiana University)

  • E. S. Anton

    (University of North Carolina)

  • Bo Li

    (Watson School of Biological Sciences, Cold Spring Harbor Laboratory)

  • Akira Sawa

    (Johns Hopkins University
    Johns Hopkins University)

Abstract

Neuregulin-1 (NRG1) and its receptor ErbB4 influence several processes of neurodevelopment, but the mechanisms regulating this signalling in the mature brain are not well known. DISC1 is a multifunctional scaffold protein that mediates many cellular processes. Here we present a functional relationship between DISC1 and NRG1-ErbB4 signalling in mature cortical interneurons. By cell type-specific gene modulation in vitro and in vivo including in a mutant DISC1 mouse model, we demonstrate that DISC1 inhibits NRG1-induced ErbB4 activation and signalling. This effect is likely mediated by competitive inhibition of binding of ErbB4 to PSD95. Finally, we show that interneuronal DISC1 affects NRG1-ErbB4-mediated phenotypes in the fast spiking interneuron-pyramidal neuron circuit. Post-mortem brain analyses and some genetic studies have reported interneuronal deficits and involvement of the DISC1, NRG1 and ErbB4 genes in schizophrenia, respectively. Our results suggest a mechanism by which cross-talk between DISC1 and NRG1-ErbB4 signalling may contribute to these deficits.

Suggested Citation

  • Saurav Seshadri & Travis Faust & Koko Ishizuka & Kristen Delevich & Youjin Chung & Sun-Hong Kim & Martis Cowles & Minae Niwa & Hanna Jaaro-Peled & Toshifumi Tomoda & Cary Lai & E. S. Anton & Bo Li & A, 2015. "Interneuronal DISC1 regulates NRG1-ErbB4 signalling and excitatory–inhibitory synapse formation in the mature cortex," Nature Communications, Nature, vol. 6(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms10118
    DOI: 10.1038/ncomms10118
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms10118
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms10118?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
    ---><---

    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_ncomms10118. 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.