Biology Reference
In-Depth Information
Figure 2. Schematic representation of regulation of CaMKII.
A
, Signal transduction of
CaMKII.CaMKII has diverse functions in the nervous system based on the various categories of
substrates and interacting proteins.Target molecules change
via
phosphorylation and/or association with
CaMKII.Then, physiological reactions progress.
B
, Association of CaMKII and its target molecules
well characterized in the presynaptic terminal and PSD of glutamatergic neurons. Although there are a
great number of CaMKII targets, only well characterized molecules are shown. Note; In the nerve
terminals of dopaminergic, noradrenergic, and serotonergic neurons, the rate-limiting enzymes of
transmitter biosynthesis (TH and TPH) are phosphorylated by CaMKII, and neurotransmitter synthesis
is increased (not shown).Red letter, CaMKII substrate; blue letter, CaMKII-interacting protein; blue
arrow, phosphorylation-dependent translocation of CaMKII and AMPA receptor.
When a nerve impulse reaches the nerve terminals, local concentration of Ca
2+
increases, and
then CaKII phosphorylates synaptic vesicle proteins and microtubule proteins.
Simultaneously, CaMKII is autophosphorylated at Thr286 and interacts with syntaxin in the
plasma membrane, and then the neurotransmitter glutamate is released into the synaptic cleft
by exocytosis. Glutamate binds to the AMPA receptor, and then the NMDA receptor is fully
activated. Ca
2+
enters postsynaptic cells through the NMDA receptor, binds calmodulin, and
activates CaMKII. The activated CaMKII is autophosphorylated at Thr286 and translocated to
the PSD, where it phosphorylates various PSD proteins. At the same time, the activated
CaMKII also phosphorylates various proteins in postsynaptic cells. Arc potentiates CaMKII
function. CaMKII also regulates gene expression and translation through the phosphorylation
