IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms9362.html
   My bibliography  Save this article

Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function

Author

Listed:
  • Karzan Muhammad

    (Freie Universität Berlin, Institute for Biology/Genetics
    NeuroCure, Charité
    Present address: Max Planck Institute for Brain Research, Neocortical Circuits Lab, Max-von-Laue-Str. 4, 60438 Frankfurt, Germany)

  • Suneel Reddy-Alla

    (Freie Universität Berlin, Institute for Biology/Genetics
    NeuroCure, Charité)

  • Jan H Driller

    (Freie Universität Berlin, Institut für Chemie und Biochemie /Strukturbiochmie)

  • Dietmar Schreiner

    (Biozentrum, University of Basel)

  • Ulises Rey

    (NeuroCure, Charité)

  • Mathias A. Böhme

    (NeuroCure, Charité)

  • Christina Hollmann

    (NeuroCure, Charité)

  • Niraja Ramesh

    (Freie Universität Berlin, Institute for Biology/Genetics)

  • Harald Depner

    (Freie Universität Berlin, Institute for Biology/Genetics
    NeuroCure, Charité)

  • Janine Lützkendorf

    (NeuroCure, Charité)

  • Tanja Matkovic

    (Freie Universität Berlin, Institute for Biology/Genetics
    NeuroCure, Charité)

  • Torsten Götz

    (Freie Universität Berlin, Institute for Biology/Genetics
    NeuroCure, Charité)

  • Dominique D. Bergeron

    (NeuroCure, Charité)

  • Jan Schmoranzer

    (Freie Universität Berlin, Institut für Chemie und Biochemie /Strukturbiochmie
    Leibniz Institut für Molekulare Pharmakologie)

  • Fabian Goettfert

    (Max Planck Institute for Biophysical Chemistry)

  • Mathew Holt

    (VIB Center for the Biology of Disease)

  • Markus C. Wahl

    (Freie Universität Berlin, Institut für Chemie und Biochemie /Strukturbiochmie)

  • Stefan W. Hell

    (Max Planck Institute for Biophysical Chemistry)

  • Peter Scheiffele

    (Biozentrum, University of Basel)

  • Alexander M. Walter

    (NeuroCure, Charité
    Leibniz Institut für Molekulare Pharmakologie)

  • Bernhard Loll

    (Freie Universität Berlin, Institut für Chemie und Biochemie /Strukturbiochmie)

  • Stephan J. Sigrist

    (Freie Universität Berlin, Institute for Biology/Genetics
    NeuroCure, Charité)

Abstract

Assembly and maturation of synapses at the Drosophila neuromuscular junction (NMJ) depend on trans-synaptic neurexin/neuroligin signalling, which is promoted by the scaffolding protein Syd-1 binding to neurexin. Here we report that the scaffold protein spinophilin binds to the C-terminal portion of neurexin and is needed to limit neurexin/neuroligin signalling by acting antagonistic to Syd-1. Loss of presynaptic spinophilin results in the formation of excess, but atypically small active zones. Neuroligin-1/neurexin-1/Syd-1 levels are increased at spinophilin mutant NMJs, and removal of single copies of the neurexin-1, Syd-1 or neuroligin-1 genes suppresses the spinophilin-active zone phenotype. Evoked transmission is strongly reduced at spinophilin terminals, owing to a severely reduced release probability at individual active zones. We conclude that presynaptic spinophilin fine-tunes neurexin/neuroligin signalling to control active zone number and functionality, thereby optimizing them for action potential-induced exocytosis.

Suggested Citation

  • Karzan Muhammad & Suneel Reddy-Alla & Jan H Driller & Dietmar Schreiner & Ulises Rey & Mathias A. Böhme & Christina Hollmann & Niraja Ramesh & Harald Depner & Janine Lützkendorf & Tanja Matkovic & Tor, 2015. "Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function," Nature Communications, Nature, vol. 6(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9362
    DOI: 10.1038/ncomms9362
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms9362
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms9362?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_ncomms9362. 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.