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Proc Natl Acad Sci U S A. 1988 Jul; 85(14): 5320–5324.
PMCID: PMC281742

Feasibility of long-term storage of graded information by the Ca2+/calmodulin-dependent protein kinase molecules of the postsynaptic density.


The feasibility of long-term information storage by brain type II Ca2+/calmodulin-dependent protein kinase molecules is explored. Recent evidence indicates that this protein has switch-like properties. Equations are derived showing that a single kinase holoenzyme could form a bistable switch having the stability necessary to encode long-term memory, and that a group of kinase molecules, such as that contained within the postsynaptic density, could form a device capable of storing graded information.

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  • Goelet P, Castellucci VF, Schacher S, Kandel ER. The long and the short of long-term memory--a molecular framework. Nature. 322(6078):419–422. [PubMed]
  • Crick F. Memory and molecular turnover. Nature. 1984 Nov 8;312(5990):101–101. [PubMed]
  • Lisman JE. A mechanism for memory storage insensitive to molecular turnover: a bistable autophosphorylating kinase. Proc Natl Acad Sci U S A. 1985 May;82(9):3055–3057. [PMC free article] [PubMed]
  • Kuret J, Schulman H. Mechanism of autophosphorylation of the multifunctional Ca2+/calmodulin-dependent protein kinase. J Biol Chem. 1985 May 25;260(10):6427–6433. [PubMed]
  • Saitoh T, Schwartz JH. Phosphorylation-dependent subcellular translocation of a Ca2+/calmodulin-dependent protein kinase produces an autonomous enzyme in Aplysia neurons. J Cell Biol. 1985 Mar;100(3):835–842. [PMC free article] [PubMed]
  • Miller SG, Kennedy MB. Regulation of brain type II Ca2+/calmodulin-dependent protein kinase by autophosphorylation: a Ca2+-triggered molecular switch. Cell. 1986 Mar 28;44(6):861–870. [PubMed]
  • Kennedy MB, Bennett MK, Erondu NE. Biochemical and immunochemical evidence that the "major postsynaptic density protein" is a subunit of a calmodulin-dependent protein kinase. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7357–7361. [PMC free article] [PubMed]
  • Goldenring JR, McGuire JS, Jr, DeLorenzo RJ. Identification of the major postsynaptic density protein as homologous with the major calmodulin-binding subunit of a calmodulin-dependent protein kinase. J Neurochem. 1984 Apr;42(4):1077–1084. [PubMed]
  • Kelly PT, McGuinness TL, Greengard P. Evidence that the major postsynaptic density protein is a component of a Ca2+/calmodulin-dependent protein kinase. Proc Natl Acad Sci U S A. 1984 Feb;81(3):945–949. [PMC free article] [PubMed]
  • Goldenring JR, Gonzalez B, McGuire JS, Jr, DeLorenzo RJ. Purification and characterization of a calmodulin-dependent kinase from rat brain cytosol able to phosphorylate tubulin and microtubule-associated proteins. J Biol Chem. 1983 Oct 25;258(20):12632–12640. [PubMed]
  • Wenderoth MP, Eisenberg BR. Incorporation of nascent myosin heavy chains into thick filaments of cardiac myocytes in thyroid-treated rabbits. J Cell Biol. 1987 Dec;105(6 Pt 1):2771–2780. [PMC free article] [PubMed]
  • Lai Y, Nairn AC, Gorelick F, Greengard P. Ca2+/calmodulin-dependent protein kinase II: identification of autophosphorylation sites responsible for generation of Ca2+/calmodulin-independence. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5710–5714. [PMC free article] [PubMed]
  • Kudo Y, Ogura A. Glutamate-induced increase in intracellular Ca2+ concentration in isolated hippocampal neurones. Br J Pharmacol. 1986 Sep;89(1):191–198. [PMC free article] [PubMed]
  • Lai Y, Nairn AC, Greengard P. Autophosphorylation reversibly regulates the Ca2+/calmodulin-dependence of Ca2+/calmodulin-dependent protein kinase II. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4253–4257. [PMC free article] [PubMed]
  • Kennedy MB, McGuinness T, Greengard P. A calcium/calmodulin-dependent protein kinase from mammalian brain that phosphorylates Synapsin I: partial purification and characterization. J Neurosci. 1983 Apr;3(4):818–831. [PubMed]
  • Huang CY, Chau V, Chock PB, Wang JH, Sharma RK. Mechanism of activation of cyclic nucleotide phosphodiesterase: requirement of the binding of four Ca2+ to calmodulin for activation. Proc Natl Acad Sci U S A. 1981 Feb;78(2):871–874. [PMC free article] [PubMed]
  • Pifl C, Plank B, Wyskovsky W, Bertel O, Hellmann G, Suko J. Calmodulin X (Ca2+)4 is the active calmodulin-calcium species activating the calcium-, calmodulin-dependent protein kinase of cardiac sarcoplasmic reticulum in the regulation of the calcium pump. Biochim Biophys Acta. 1984 Jun 27;773(2):197–206. [PubMed]
  • Blomberg F, Cohen RS, Siekevitz P. The structure of postsynaptic densities isolated from dog cerebral cortex. II. Characterization and arrangement of some of the major proteins within the structure. J Cell Biol. 1977 Jul;74(1):204–225. [PMC free article] [PubMed]
  • Kelly PT, Yip RK, Shields SM, Hay M. Calmodulin-dependent protein phosphorylation in synaptic junctions. J Neurochem. 1985 Nov;45(5):1620–1634. [PubMed]
  • Collingridge GL, Kehl SJ, McLennan H. Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus. J Physiol. 1983 Jan;334:33–46. [PMC free article] [PubMed]
  • Harris EW, Ganong AH, Cotman CW. Long-term potentiation in the hippocampus involves activation of N-methyl-D-aspartate receptors. Brain Res. 1984 Dec 3;323(1):132–137. [PubMed]
  • Lynch G, Larson J, Kelso S, Barrionuevo G, Schottler F. Intracellular injections of EGTA block induction of hippocampal long-term potentiation. Nature. 1983 Oct 20;305(5936):719–721. [PubMed]
  • MacDermott AB, Mayer ML, Westbrook GL, Smith SJ, Barker JL. NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones. Nature. 321(6069):519–522. [PubMed]
  • Morris RG, Anderson E, Lynch GS, Baudry M. Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature. 319(6056):774–776. [PubMed]

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