title: In vitro reconstitution of a CaMKII memory switch by an NMDA receptor-derived peptide.
abstract: Ca(2+)/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 Ca(2+)/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 Ca(2+) range of hysteresis. These functions may be crucial for induction and maintenance of long-term synaptic plasticity at hippocampal synapses.
authors.affiliation: Department of Systems Science, Graduate School of Informatics, Kyoto University, Kyoto, Japan; Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan. Electronic address: urakubo-h@sys.i.kyoto-u.ac.jp.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Urakubo
authors.affiliation: Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Miharu
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Systems Science, Graduate School of Informatics, Kyoto University, Kyoto, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Ishii
authors.affiliation: Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan. Electronic address: skuroda@bi.s.u-tokyo.ac.jp.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kuroda
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D054645:Protein Phosphatase 1 / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000378:metabolism*; D061987:Sf9 Cells; D018411:Spodoptera
chemical_list: C121001:NR2B NMDA receptor; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D054645:Protein Phosphatase 1; D002118:Calcium