Abstract
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.
Full text
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Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Blomberg F., Cohen R. S., 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. doi: 10.1083/jcb.74.1.204. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Collingridge G. L., Kehl S. J., 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. doi: 10.1113/jphysiol.1983.sp014478. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crick F. Memory and molecular turnover. Nature. 1984 Nov 8;312(5990):101–101. doi: 10.1038/312101a0. [DOI] [PubMed] [Google Scholar]
- Goelet P., Castellucci V. F., Schacher S., Kandel E. R. The long and the short of long-term memory--a molecular framework. 1986 Jul 31-Aug 6Nature. 322(6078):419–422. doi: 10.1038/322419a0. [DOI] [PubMed] [Google Scholar]
- Goldenring J. R., Gonzalez B., McGuire J. S., Jr, DeLorenzo R. J. 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] [Google Scholar]
- Goldenring J. R., McGuire J. S., Jr, DeLorenzo R. J. 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. doi: 10.1111/j.1471-4159.1984.tb12713.x. [DOI] [PubMed] [Google Scholar]
- Harris E. W., Ganong A. H., Cotman C. W. Long-term potentiation in the hippocampus involves activation of N-methyl-D-aspartate receptors. Brain Res. 1984 Dec 3;323(1):132–137. doi: 10.1016/0006-8993(84)90275-0. [DOI] [PubMed] [Google Scholar]
- Huang C. Y., Chau V., Chock P. B., Wang J. H., Sharma R. K. 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. doi: 10.1073/pnas.78.2.871. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kelly P. T., McGuinness T. L., 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. doi: 10.1073/pnas.81.3.945. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kelly P. T., Yip R. K., Shields S. M., Hay M. Calmodulin-dependent protein phosphorylation in synaptic junctions. J Neurochem. 1985 Nov;45(5):1620–1634. doi: 10.1111/j.1471-4159.1985.tb07235.x. [DOI] [PubMed] [Google Scholar]
- Kennedy M. B., Bennett M. K., Erondu N. E. 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. doi: 10.1073/pnas.80.23.7357. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kennedy M. B., 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. doi: 10.1523/JNEUROSCI.03-04-00818.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kudo Y., Ogura A. Glutamate-induced increase in intracellular Ca2+ concentration in isolated hippocampal neurones. Br J Pharmacol. 1986 Sep;89(1):191–198. doi: 10.1111/j.1476-5381.1986.tb11135.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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] [Google Scholar]
- Lai Y., Nairn A. C., 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. doi: 10.1073/pnas.84.16.5710. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lai Y., Nairn A. C., 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. doi: 10.1073/pnas.83.12.4253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lisman J. E. 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. doi: 10.1073/pnas.82.9.3055. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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. doi: 10.1038/305719a0. [DOI] [PubMed] [Google Scholar]
- MacDermott A. B., Mayer M. L., Westbrook G. L., Smith S. J., Barker J. L. NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones. 1986 May 29-Jun 4Nature. 321(6069):519–522. doi: 10.1038/321519a0. [DOI] [PubMed] [Google Scholar]
- Miller S. G., Kennedy M. B. 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. doi: 10.1016/0092-8674(86)90008-5. [DOI] [PubMed] [Google Scholar]
- Morris R. G., Anderson E., Lynch G. S., Baudry M. Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. 1986 Feb 27-Mar 5Nature. 319(6056):774–776. doi: 10.1038/319774a0. [DOI] [PubMed] [Google Scholar]
- 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. doi: 10.1016/0005-2736(84)90083-x. [DOI] [PubMed] [Google Scholar]
- Saitoh T., Schwartz J. H. 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. doi: 10.1083/jcb.100.3.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wenderoth M. P., Eisenberg B. R. 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. doi: 10.1083/jcb.105.6.2771. [DOI] [PMC free article] [PubMed] [Google Scholar]