A mechanism for Ca2+/calmodulin-dependent protein kinase II clustering at synaptic and nonsynaptic sites based on self-association

Andy Hudmon, Eric LeBel, Hugo Roy, Attila Sik, Howard Schulman, M. Neal Waxham, Paul De Koninck

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

The activity of Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays an integral role in regulating synaptic development and plasticity. We designed a live-cell-imaging approach to monitor an activity-dependent clustering of green fluorescent protein (GFP)-CaMKII holoenzymes, termed self-association, a process that we hypothesize contributes to the translocation of CaMKII to synaptic and nonsynaptic sites in activated neurons. We show that GFP-CaMKII self-association in human embryonic kidney 293 (HEK293) cells requires a catalytic domain and multimeric structure, requires Ca2+ stimulation and a functional Ca2+/CaM-binding domain, is regulated by cellular pH and Thr286 autophosphorylation, and has variable rates of dissociation depending on Ca2+ levels. Furthermore, we show that the same rules that govern CaMKII self-association in HEK293 cells apply for extrasynaptic and postsynaptic translocation of GFP-CaMKII in hippocampal neurons. Our data support a novel mechanism for targeting CaMKII to postsynaptic sites after neuronal activation. As such, CaMKII may form a scaffold that, in combination with other synaptic proteins, recruits and localizes additional proteins to the postsynaptic density. We discuss the potential function of CaMKII self-association as a tag of synaptic activity.

Original languageEnglish (US)
Pages (from-to)6971-6983
Number of pages13
JournalJournal of Neuroscience
Volume25
Issue number30
DOIs
StatePublished - Jul 27 2005
Externally publishedYes

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Calcium-Calmodulin-Dependent Protein Kinase Type 2
Cluster Analysis
Green Fluorescent Proteins
Kidney
Neurons
Holoenzymes
Neuronal Plasticity
Catalytic Domain

Keywords

  • Aggregation
  • Autophosphorylation
  • Calmodulin
  • Postsynaptic density
  • Protein translocation
  • Synaptic tag

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

A mechanism for Ca2+/calmodulin-dependent protein kinase II clustering at synaptic and nonsynaptic sites based on self-association. / Hudmon, Andy; LeBel, Eric; Roy, Hugo; Sik, Attila; Schulman, Howard; Waxham, M. Neal; De Koninck, Paul.

In: Journal of Neuroscience, Vol. 25, No. 30, 27.07.2005, p. 6971-6983.

Research output: Contribution to journalArticle

Hudmon, Andy ; LeBel, Eric ; Roy, Hugo ; Sik, Attila ; Schulman, Howard ; Waxham, M. Neal ; De Koninck, Paul. / A mechanism for Ca2+/calmodulin-dependent protein kinase II clustering at synaptic and nonsynaptic sites based on self-association. In: Journal of Neuroscience. 2005 ; Vol. 25, No. 30. pp. 6971-6983.
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