In vitro reconstitution of a CaMKII memory switch by an NMDA receptor-derived peptide

Hidetoshi Urakubo, Miharu Sato, Shin Ishii, Shinya Kuroda

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20 Citations (Scopus)


Ca2+/Calmodulin-dependent protein kinase II (CaMKII) has been shown to play a major role in establishing memories through complex molecular interactions including phosphorylation of multiple synaptic targets. However, it is still controversial whether CaMKII itself serves as a molecular memory because of a lack of direct evidence. Here, we show that a single holoenzyme of CaMKII per se serves as an erasable molecular memory switch. We reconstituted Ca2+/Calmodulin-dependent CaMKII autophosphorylation in the presence of protein phosphatase 1 in vitro, and found that CaMKII phosphorylation shows a switch-like response with history dependence (hysteresis) only in the presence of an N-methyl-D-aspartate receptor-derived peptide. This hysteresis is Ca 2+ and protein phosphatase 1 concentration-dependent, indicating that the CaMKII memory switch is not simply caused by an N-methyl-D-aspartate receptor-derived peptide lock of CaMKII in an active conformation. Mutation of a phosphorylation site of the peptide shifted the Ca2+ range of hysteresis. These functions may be crucial for induction and maintenance of long-term synaptic plasticity at hippocampal synapses.

Original languageEnglish
Pages (from-to)1414-1420
Number of pages7
JournalBiophysical Journal
Issue number6
Publication statusPublished - 18-03-2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics


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