IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v411y2001i6839d10.1038_35081080.html
   My bibliography  Save this article

Interaction with the NMDA receptor locks CaMKII in an active conformation

Author

Listed:
  • K.-Ulrich Bayer

    (Stanford University School of Medicine)

  • Paul De Koninck

    (Stanford University School of Medicine
    Centre de Recherche Université Laval Robert-Giffard)

  • A. Soren Leonard

    (University of Wisconsin
    University of Iowa)

  • Johannes W. Hell

    (University of Wisconsin
    University of Iowa)

  • Howard Schulman

    (Stanford University School of Medicine)

Abstract

Calcium- and calmodulin-dependent protein kinase II (CaMKII) and glutamate receptors are integrally involved in forms of synaptic plasticity that may underlie learning and memory. In the simplest model for long-term potentiation1, CaMKII is activated by Ca2+ influx through NMDA (N-methyl-d-aspartate) receptors and then potentiates synaptic efficacy by inducing synaptic insertion2,3 and increased single-channel conductance4 of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. Here we show that regulated CaMKII interaction with two sites on the NMDA receptor subunit NR2B provides a mechanism for the glutamate-induced translocation of the kinase to the synapse in hippocampal neurons. This interaction can lead to additional forms of potentiation by: facilitated CaMKII response to synaptic Ca2+; suppression of inhibitory autophosphorylation of CaMKII; and, most notably, direct generation of sustained Ca2+/calmodulin (CaM)-independent (autonomous) kinase activity by a mechanism that is independent of the phosphorylation state. Furthermore, the interaction leads to trapping of CaM that may reduce down-regulation of NMDA receptor activity5. CaMKII–NR2B interaction may be prototypical for direct activation of a kinase by its targeting protein.

Suggested Citation

  • K.-Ulrich Bayer & Paul De Koninck & A. Soren Leonard & Johannes W. Hell & Howard Schulman, 2001. "Interaction with the NMDA receptor locks CaMKII in an active conformation," Nature, Nature, vol. 411(6839), pages 801-805, June.
    • Handle: RePEc:nat:nature:v:411:y:2001:i:6839:d:10.1038_35081080
    DOI: 10.1038/35081080
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/35081080
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/35081080?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.

    Citations

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


    Cited by:

    1. Fares J. P. Sayegh & Lionel Mouledous & Catherine Macri & Juliana Pi Macedo & Camille Lejards & Claire Rampon & Laure Verret & Lionel Dahan, 2024. "Ventral tegmental area dopamine projections to the hippocampus trigger long-term potentiation and contextual learning," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. Tuan A. Nguyen & Henry L. Puhl & Kirk Hines & Daniel J. Liput & Steven S. Vogel, 2022. "Binary-FRET reveals transient excited-state structure associated with activity-dependent CaMKII - NR2B binding and adaptation," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Paul Miller & Anatol M Zhabotinsky & John E Lisman & Xiao-Jing Wang, 2005. "The Stability of a Stochastic CaMKII Switch: Dependence on the Number of Enzyme Molecules and Protein Turnover," PLOS Biology, Public Library of Science, vol. 3(4), pages 1-1, March.

    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:411:y:2001:i:6839:d:10.1038_35081080. 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.