Biology Reference
In-Depth Information
al., 1985). The concentration of α and β proteins varies markedly in brain regions with age in
the postnatal period. In early postnatal brain, the concentration of these proteins is low, and
increases 20-60 fold between day 10 and 30 dependent on the region, indicating that the
kinase is specifically expressed during the most active period in the formation of the synaptic
network (Sugiura & Yamauchi, 1992).The expression of many substrates of CaMKII is also
regulated developmentally, with levels increasing from neonates to adults according to the
increase in the amount of CaMKII (Sugiura & Yamauchi, 1994).
The expression of α and β CaMKII is carefully regulated at the level of transcription.
The α and β CaMKII genes both have strong transcriptional activity in the 5'-flanking region,
but have no sequence identity or similarity in this region (Donai et al. 2001; Mima et al.,
2001). Zic2, a zinc finger transcription factor, and rLRP157, rat leucine-rich protein 157 kDa
protein, have been identified as one of the promoter-binding and activating proteins of α and
β CaMKII, respectively (Sakurada et al., 2005; Ochiai et al.,
2007). Some other promoter-
binding proteins are found in the nuclear extract of the brain and should be identified.
2-4. Translocation in subcellular distribution
Autophosphorylation-dependent reversible translocation of α CaMKII to the PSD is
important to the signal transduction in postsynaptic cells as described in a later section
(Section 5-2).
(3)
I
NVOLVEMENT OF
C
A
MKII
IN
P
LASTICITY AND
/
OR
L
EARNING
AND
M
EMORY IN
A
NIMAL AND
C
ELL
M
ODELS
A large number of extracellular signals have been shown to regulate protein
phosphorylation in the nervous system. Genetic approaches, including the use of various
mutant mice, have provided a wealth of information on the role of CaMKII and cognition
(Elgersma et al., 2004). Cell models are also useful because of their high reproducibility and
ease of handling.
3-1. CaMKII null mutant mice
Neuronal CaMKII was first recognized as involved in learning and memory based on the
report that transgenic mice lacking the α isoform are defective in LTP in the hippocampus
and spatial learning (Silva et al., 1992). Follow-up studies were carried out using subsequent
generations of these mutant mice in a novel inbred background. Although LTP at 60 min
post-tetanus is clearly deficient in these α CaMKII null mutant mice compared with α
CaMKII control animals, the mutants mice do show a significant level of LTP. The amount of
LTP observed in α CaMKII mutants is normally distributed and does not correlate with age
(Hinds et al. 1998). The experience-dependent plasticity of the barrel cortex is also prevented
in adult mice that lack the gene encoding α CaMKII, indicating that α CaMKII is necessary
