IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms5058.html
   My bibliography  Save this article

ADAM metalloproteases promote a developmental switch in responsiveness to the axonal repellant Sema3A

Author

Listed:
  • Erez Romi

    (Weizmann Institute of Science)

  • Irena Gokhman

    (Weizmann Institute of Science)

  • Eitan Wong

    (Weizmann Institute of Science)

  • Niv Antonovsky

    (Weizmann Institute of Science)

  • Andreas Ludwig

    (Institute for Pharmacology and Toxicology, RWTH Aachen University)

  • Irit Sagi

    (Weizmann Institute of Science)

  • Paul Saftig

    (Institut fur Biochemie, Christian-Albrechts-Universität)

  • Marc Tessier-Lavigne

    (Laboratory of Brain Development and Repair, Rockefeller University)

  • Avraham Yaron

    (Weizmann Institute of Science)

Abstract

During embryonic development, axons can gain and lose sensitivity to guidance cues, and this flexibility is essential for the correct wiring of the nervous system. Yet, the underlying molecular mechanisms are largely unknown. Here we show that receptor cleavage by ADAM (A Disintegrin And Metalloprotease) metalloproteases promotes murine sensory axons loss of responsiveness to the chemorepellant Sema3A. Genetic ablation of ADAM10 and ADAM17 disrupts the developmental downregulation of Neuropilin-1 (Nrp1), the receptor for Sema3A, in sensory axons. Moreover, this is correlated with gain of repulsive response to Sema3A. Overexpression of Nrp1 in neurons reverses axonal desensitization to Sema3A, but this is hampered in a mutant Nrp1 with high susceptibility to cleavage. Lastly, we detect guidance errors of proprioceptive axons in ADAM knockouts that are consistent with enhanced response to Sema3A. Our results provide the first evidence for involvement of ADAMs in regulating developmental switch in responsiveness to axonal guidance cues.

Suggested Citation

  • Erez Romi & Irena Gokhman & Eitan Wong & Niv Antonovsky & Andreas Ludwig & Irit Sagi & Paul Saftig & Marc Tessier-Lavigne & Avraham Yaron, 2014. "ADAM metalloproteases promote a developmental switch in responsiveness to the axonal repellant Sema3A," Nature Communications, Nature, vol. 5(1), pages 1-15, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5058
    DOI: 10.1038/ncomms5058
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms5058
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms5058?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:5:y:2014:i:1:d:10.1038_ncomms5058. 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.