Abstract
In the mammalian brain, the hippocampus is involved in memory formation and storage and has an enriched level of Ca2+/calmodulin-dependent protein kinase type II (CaM kinase II). CaM kinase II has a number of downstream targets and is shown to play a role in memory development, axonal transport, and signaling across the synapse. The shiverer mutant mouse is a knockout lacking myelin basic protein. As a result, the axons of the central nervous system (CNS) of the shiverer have no or very thin myelin sheath, neurons in their CNS have distorted shapes, and synaptic signaling is impaired. shiverer mice develop symptoms similar to those experienced by patients with multiple sclerosis. In this study, proteins from the hippocampus, cerebellum, pons, medulla, and olfactory bulbs of shiverer and wild-type mice were extracted. Western blot analysis was used to compare the expression levels of CaM kinase II in these regions of the two types of mice. Analysis shows that at least two (50 and 58–59 kDa) of the four CaM kinase II isoforms are expressed in the brain, with one isoform (50 kDa) expressed in all regions examined. shiverer brain contains a decreased level of the two isoforms of CaM kinase II, an indication that the cognitive function of these mice might also be impaired.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Derkach V., Barria A., and Soderling T. R. (1999) Ca2+/calmodulin-kinase II enhances channel conductance of alpha-amino-3-hydroxy-5-methyl-isoxazolepropionate type glutamate receptors. Proc. Natl. Acad. Sci. U. S. A. 96, 500–503.
Dupouey P., Jacque C., Bourre J. M., Cesselin F., Privat A., and Baumann N. (1979) Immunochemical studies of myelin basic protein in shiverer mouse devoid of major dense line of myelin. Neurosci. Lett. 12, 113–118.
Dyer C. A., Phillbotte T., Wolf M. K., and Billings-Gagliardi S. (1997) Regulation of cytoskeleton by myelin components: studies on shiverer oligodendrocytes carrying an Mbp transgene. Dev. Neurosci. 19, 395–409.
Fink C. C., Bayer K.-U., Myers J. W., Ferrell J. E., Schulman H., and Meyer T. (2003) Selective regulation of neurite extension and synapse formation by the β but not the α isoform of CaM kinase II. Neuron 39, 283–297.
Gaertner T. R., Kolodziej S. J., Wang D., Kobayashi R., Koomen J. M., Stoops J. K., and Waxham M. N. (2004) Comparative analyses of the three-dimensional structures and enzymatic properties of α, β, γ, and δ isoforms of Ca2+-calmodulin-dependent protein kinase II. J. Biol. Chem. 279, 12,484–12,494.
Gupta R. P., Lapadula D. M., and Abou-Donia M. B. (1992) Ca2+/calmodulin-dependent protein kinase II from hen brain. Purification and characterization. Biochem. Pharmacol. 43, 1975–1988.
Kirkpatrick L., Witt A. S., Payne H. R., Shine H. D., and Brady S. T. (2001) Changes in microtubule stability and density in myelin-deficient shiverer mouse CNS axons. J. Neurosci. 21, 2288–2297.
Lee H. K., Choi S. S., Han E. J., Han K. J., and Suh H. W. (2003) Role of glutamate receptors and an ongoing protein synthesis in the regulation of phosphorylation of Ca2+/calmodulin-dependent protein kinase II in the CA3 hippocampal region in mice administered with kainic acid intracerebroventricularly. Neurosci. Lett. 348, 93–96.
Leonard A., Soren I., Lim A., Hemsworth D. E., Horne M. C., and Hell J. W. (1999) Calcium/calmodulin-dependent protein kinase II is associated with the N-methyl-D-aspartate receptor. Proc. Natl. Acad. Sci. U. S. A. 96, 3239–3244.
Mikoshiba K., Kohsaka S., Takamatsu K., and Taukada Y. (1981) Neurochemical and morphological studies on the myelin of peripheral nervous system from Shiverer mutant mice: absence of basic proteins common to central nervous system. Brain Res. 204, 455–460.
Patton B. L., Malloy S. S., and Kennedy M. B. (1993) Autophosphorylation of type II CaM kinase inhippocampal neurons: localizations of phospho-and dephosphokinase with complementary phosphorylation site-specific antibodies. Mol. Biol. Cell 4, 159–172.
Roach A., Takahashi N., Pravtcheva D., Ruddle F., and Hood L. E. (1983) Characterization of cloned cDNA representing rat myelin basic protein: absence of expression in brain of shiverer mutant mice. Cell 34, 799–806.
Sadahiro S., Yoshikawa H., Yagi N., Yamamoto Y., Yanagihara T., Kimura M., and Sakoda S. (2000) Morphometric analysis of the myelin-associated oligodendrocytic basic protein-deficient mouse reveals a possible role for myelin-associated oligodendrocytic basic protein in regulating axonal diameter. Neuroscience 98, 361–367.
Schulman H. The multifunctional Ca2+/calmodulin-dependent protein kinases. (1993) Curr. Opin. Cell Biol. 5, 247–253.
Seiwa C., Kojima-Aikawa K., Matsumoto I., and Asou H. (2002) CNS myelinogenesis in vitro: myelin basic protein deficient shiverer oligodendrocytes. J. Neurosci. Res. 69, 305–317.
Strack S., McNeill R. B., and Colbran R. I. (2000) Mechanismand regulation of calcium/calmodulin-dependent protein kinase II targeting to the NR2B isoform of the N-methyl-D-aspartate receptor. J. Biol. Chem. 275, 798–806.
Uschkureit T., Sporkel O., Strackel J., Bousssow H., and Stoffel W. (2000) Early onset of axonal degeneration in double (plp-/-mag-/-) and hypermyelinosis in triple (plp-/-mbp-/-mag-/) mutant mice. J. Neurosci. 20, 5225–5233.
Vallano M. L. (1988) Identification and regional distribution of a type II calcium/calmodulin-dependent kinase in mouse brain. Biochem. Pharmacol. 37, 2381–2388.
Weeber E. J., Jiang Y.-H., Elgersma Y., Varga A. W., Carrasquillo Y., Brown S. E., et al. (2003) Derangements of hippocampal calcium/calmodulin-dependent protein kinase II in a mouse model for Angelman mental retardation syndrome. J. Neurosci. 23, 2634–2644.
Yamauchi T., Yoshimura Y., Nomura T., Fujii M., and Sugirua H. (1998) Neurite outgrowth of neuroblastoma cells overexpressing α and β isotorms of Ca2+/calmodulin-dependent protein kinase II—effects of protein kinase inhibitors. Brain Res. Protocols 2, 250–258.
Yanagisawa M., Planel E., Ishiguro K., and Fujita S. C. (1993) Starvation induces tau phosphorylation in mouse brain: implications for Alzheimer’s disease. FEBS Lett. 461, 329–333.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Suznovich, C.T., Pu, R. & Bieber, A.J. CaM kinase II isoforms are expressed at lower levels in brains of shiverer mutants. J Mol Neurosci 31, 297–305 (2007). https://doi.org/10.1385/JMN:31:03:297
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1385/JMN:31:03:297