Neuronal Ca2+/Calmodulin-Dependent Protein Kinase II-Discovery, Progress in a Quarter of a Century, and Perspective: Implication for Learning and Memory

Abstract

Much has been learned about the activity-dependent synaptic modifications that are thought to underlie memory storage, but the mechanism by which these modifications are stored remains unclear. A good candidate for the storage mechanism is Ca 2؉ /calmodulin-dependent protein kinase II (CaM kinase II). CaM kinase II is one of the most prominent protein kinases, present in essentially every tissue but most concentrated in brain. Although it has been about a quarter of a century since the finding, CaM kinase II has been of the major interest in the region of brain science. It plays a multifunctional role in many intracellular events, and the expression of the enzyme is carefully regulated in brain regions and during brain development. Neuronal CaM kinase II regulates important neuronal functions, including neurotransmitter synthesis, neurotransmitter release, modulation of ion channel activity, cellular transport, cell morphology and neurite extension, synaptic plasticity, learning and memory, and gene expression. Studies concerning this kinase have provided insight into the molecular basis of nerve functions, especially learning and memory, and indicate one direction for studies in the field of neuroscience. This review presents the molecular structure, properties and functions of CaM kinase II, as a major component of neurons, based mainly developed on findings made in our laboratory.

A Combined Metabonomic and Proteomic Approach Identifies Frontal Cortex Changes in a Chronic Phencyclidine Rat Model in Relation to Human Schizophrenia Brain Pathology

“…The CAMK family regulates a range of processes associated with synaptic plasticity and cognition, including long-term potentiation (Fink and Meyer, 2002;Yamauchi, 2005), and has been associated previously with SCZ (Novak et al, 2006) and PCP treatment (Mouri et al, 2007b). We also found that subunits of the multifunctional calcium-dependent serine/ threonine phosphatase calcineurin A were altered in the PCP rats.…”

Conditional Neuronal Simian Virus 40 T Antigen Expression Induces Alzheimer-Like Tau and Amyloid Pathology in Mice

“…1 B) and cortex (data not shown) within 2-3 weeks off-Dox and throughout the brain (data not shown) in all lines. Consistent with CaM kinase II␣ promoter activity (Ochiishi et al, 1994;Mansuy et al, 1998;Ochiishi et al, 1998;Yamauchi, 2005), the distribution and morphology of the Tag-positive cells indicated specific expression of TAg in neurons ( Fig. 1 B).…”

The interactions of flavonoids within neuronal signalling pathways

“…Calcium dependent MAPK signalling has been suggested to play a role in glutamate receptor-mediated neuronal stress [133]. The influx of Ca 2+ into the cytosol from the extracellular space or from intracellular stores following stress stimuli may activate Ca 2+ /calmodulin kinases, which in turn can stimulate the activation of all three MAPK, especially JNK [190]. Alternatively, flavonoids may exert direct interactions with upstream signalling components required for the recruitment and activation of JNK in neurons.…”