Calcium/calmodulin-dependent protein kinase II is associated with the N- methyl-D-aspartate receptor

A. S. Leonard, I. A. Lim, D. E. Hemsworth, Mary C Horne, Johannes W Hell

Research output: Contribution to journalArticlepeer-review

314 Scopus citations

Abstract

The molecular basis of long-term potentiation (LTP), a long-lasting change in synaptic transmission, is of fundamental interest because of its implication in learning. Usually LTP depends on Ca2+ influx through postsynaptic N-methyl-D-aspartate (NMDA)-type glutamate receptors and subsequent activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). For a molecular understanding of LTP it is crucial to know how CaMKII is localized to its postsynaptic targets because protein kinases often are targeted to their substrates by adapter proteins. Here we show that CaMKII directly binds to the NMDA receptor subunits NR1 and NR2B. Moreover, activation of CaMKIIα by stimulation of NMDA receptors in forebrain slices increase this association. This interaction places CaMKII not only proximal to a major source of Ca2+ influx but also close to α-amino-3-hydroxy-5- methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors, which become phosphorylated upon stimulation of NMDA receptors in these forebrain slices. Identification of the postsynaptic adapter for CaMKII fills a critical gap in the understanding of LTP because CaMKII-mediated phosphorylation of AMPA receptors is an important step during LTP.

Original languageEnglish (US)
Pages (from-to)3239-3244
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number6
DOIs
StatePublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • General

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