IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v414y2001i6864d10.1038_414643a.html
   My bibliography  Save this article

Kinesin-mediated axonal transport of a membrane compartment containing β-secretase and presenilin-1 requires APP

Author

Listed:
  • Adeela Kamal

    (School of Medicine, University of California San Diego
    Conforma Therapeutics Corporation)

  • Angels Almenar-Queralt

    (School of Medicine, University of California San Diego)

  • James F. LeBlanc

    (Ciphergen Biosystems Inc.)

  • Elizabeth A. Roberts

    (School of Medicine, University of California San Diego)

  • Lawrence S. B. Goldstein

    (School of Medicine, University of California San Diego)

Abstract

Proteolytic processing of amyloid precursor protein (APP) generates amyloid-β peptide and has been implicated in the pathogenesis of Alzheimer's disease1. However, the normal function of APP, whether this function is related to the proteolytic processing of APP, and where this processing takes place in neurons in vivo remain unknown. We have previously shown that the axonal transport of APP in neurons is mediated by the direct binding of APP to the kinesin light chain subunit of kinesin-I, a microtubule motor protein2. Here we identify an axonal membrane compartment that contains APP, β-secretase and presenilin-1. The fast anterograde axonal transport of this compartment is mediated by APP and kinesin-I. Proteolytic processing of APP can occur in the compartment in vitro and in vivo in axons. This proteolysis generates amyloid-β and a carboxy-terminal fragment of APP, and liberates kinesin-I from the membrane. These results suggest that APP functions as a kinesin-I membrane receptor, mediating the axonal transport of β-secretase and presenilin-1, and that processing of APP to amyloid-β by secretases can occur in an axonal membrane compartment transported by kinesin-I.

Suggested Citation

  • Adeela Kamal & Angels Almenar-Queralt & James F. LeBlanc & Elizabeth A. Roberts & Lawrence S. B. Goldstein, 2001. "Kinesin-mediated axonal transport of a membrane compartment containing β-secretase and presenilin-1 requires APP," Nature, Nature, vol. 414(6864), pages 643-648, December.
    • Handle: RePEc:nat:nature:v:414:y:2001:i:6864:d:10.1038_414643a
    DOI: 10.1038/414643a
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/414643a
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/414643a?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    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:nature:v:414:y:2001:i:6864:d:10.1038_414643a. 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.