Biology Reference
In-Depth Information
In the forebrain, α CaMKII is more homogeneously distributed through cellular layers II to V
than β CaMKII (Ochiishi et al., 1994b). In the cerebellum, the α isoform is present selectively
in Purukinje cells, and a majority of the β isoform distributes in granular cells and neurons in
the cerebellar nuclei (Ichikawa et al., 1992). Regional differences of distribution between α
and β CaMKII are also shown in the retina and brainstem of rats (Ochiishi et al.,
1994a;
1998). The distribution of α CaMKII corresponds with that of choline acetyl transferase in the
retina, suggesting that the kinase participates in the regulation of the cholinergic system,
especially the “light OFF” system in the retina (Ochiishi et al., 1994a). A different
distribution of α and β isoforms is found in spinal cord of rat and monkey (Terashima et al.,
1994). α CaMKII occurs in both dorsal and ventral corticospinal tract fibers, and β CaMKII is
distributed in the neuropil of the gray matter.
2-2-2. Subcellular distribution
The subcellular localization and compartmentalization of specific proteins generally play
a significant role in the functioning of signal transduction. In brain tissue, α CaMKII is found
in the cytosolic fraction and PSD. α CaMKII is one of the major proteins in the PSD
(Kennedy et al., 1983; Goldenring et al., 1984; Kelly et al., 1984). In the hippocampus, β
CaMKII is associated with actin filaments (Shen et al., 1998).
The different subcellular distribution of α and β isoforms is demonstrated using
neuroblastoma cells overexpressing each isoform as a model system. α CaMKII is mainly
distributed in the cytosolic fraction, whereas the β isoform is in the particulate fraction
(Yamauchi et al., 1990). Deletion analysis reveals that the second part of the β-specific
insertion and oligomeric form are important to the particulate distribution of β CaMKII
(Urushihara & Yamauchi, 2001).
2-2-3. Dendritic distribution of mRNA
mRNA of α CaMKII is distributed in dendrites of the cerebral cortex (Burgin et al.,
1990).The 3' untranslated region (UTR) of α CaMKII mRNA is important to the dendritic
distribution of the kinase (Miller et al., 2002). mRNAs of some neuronal proteins, including
microtubule associated protein 2 (MAP2), calmodulin, and activity-regulated cytoskeleton-
associated protein (Arc), inositol 1,4,5-trisphosphate (IP3) receptor, and N-methyl-D-
aspartate (NMDA) receptor 2B subunit, are also found in dendrites (Steward & Schuman,
2001). It is interest that proteins translated from these mRNA are a substrate or regulating
protein of CaMKII. Dendritic distribution of mRNA is related to the activity-dependent local
protein synthesis without transcription of mRNA, and the translation of dendritic mRNAs
may be regulated by signaling events at synapses. Therefore, local protein production during
long-term synaptic plasticity has focused attention on the mechanism involved (Steward,
1997; Steward & Schuman, 2001).
2-3. Development:Relation to synaptic network formation
The levels of α and β proteins of CaMKII depend on the stage of development. There are
two developmentally regulated isoforms of the kinase in the rat forebrain with α : β ratios for
10-day and adult enzymes of 1 : 1 and 2.3 : 1, respectively (McGuinness et al., 1985; Miller et
