Biology Reference
In-Depth Information
restricted to the soma. Mutant mice show a dramatic reduction of α CaMKII in the PSD, a
reduction in late-phase LTP, and impairments in spatial memory, associative fear
conditioning, and object recognition memory. These results demonstrate that local translation
is important for synaptic delivery of the kinase and that local translation contributes to
synaptic and behavioral plasticity. The results are supported by the finding that the induction
of LTP increased the amount of α CaMKII mRNA in synaptosomes isolated from the dentate
gyrus (Hivak et al., 2003).
3-5. Neuronal cells
The involvement of CaMKII in the increase in the number of synaptic contacts was
demonstrated in pyramidal neurons (Pratt et al., 2003). Postsynaptic expression of the
activated CaMKII T286D mutant increased the strength of transmission between pairs of
pyramidal neurons, through a modest increase in quantal amplitude and a larger increase in
the number of synaptic contacts.
In the CA1 region in hippocampal slices, a CaMKII inhibitor strongly reduced synaptic
transmission. The inhibition occured in both LTP and control pathway, but only partially
recovered after removal of the inhibitor. These data support the notion that CaMKII is
involved in controlling basal synaptic strength (Sanhueza et al., 2007).
In cultures of dissociated rat hippocampal neurons, depolarization-induced secretion of
postsynaptic neurotrophin (NT) is elicited by Ca
2+
influx and inhibited in the presence of
CaMKII inhibitor, indicating a critical dependence on the activation of CaMKII (Kolarow et
al., 2007). The mammalian neurotrophins nerve growth factor (NGF), brain derived
neurotrophic factor (BDNF), NT-3, and NT-4 constitute a family of secreted neuronal growth
factors. NTs are implicated in several forms of activity-dependent synaptic plasticity. Taken
together, depolarization-induced postsynaptic NT secretion is elicited by Ca
2+
influx and
activation of CaMKII.
CaMKII regulates gene expression
via
phosphorylation of transcription factors, such as
cAMP response element-binding protein
(CREB) and NeuroD. Using neuroblstoma cells
expressing CREB and CaMKII, phosphorylation of serine 142 in CREB by CaMKII was
shown to lead to the dissociation of the CREB dimer without impeding DNA-binding
capacity. Dimeric CREB is required to recruit the CREB-binding protein (CBP). These
results suggest that CaMKII confers a dominant inhibitory effect on transcription by
preventing dimerization of CREB, and this mechanism is responsible for the attenuation of
gene expression (Wu & McMurray, 2001). The transcription factor NeuroD mediates
neuronal activity-dependent dendritogenesis. The genetic knockdown of NeuroD in primary
granule neurons of cerebellar profoundly impaired the generation and maintenance of
dendrites while sparing the development of axons. CaMKII phosphorylates NeuroD in
primary neurons, and thereby stimulates dendritic growth, indicating that CaMKII-NeuroD
signaling pathway plays important roles in synaptic plasticity in the developing and mature
brain (Gaudilliere, et al., 2004).
A cell culture model was developed by overexpressing the α and β isoforms of CaMKII
in neuroblastoma cells (Goshima et al., 1993; 99 Nomura et al., 1997). Expression of the
isoforms stimulates neurite outgrowth and growth cone motility in these cells. This
