Biology Reference
In-Depth Information
domain of myosin V, enriched in the PSD fraction. CaMKII is activated in a CaM-
independent manner via its association with myosin V after translocation to the PSD (Costa et
al., 1999). Myosin V may function for CaMKII to shuttle between the cytosol and PSD in
dendritic spines along the actin filament network. Thus, CaMKII is involved in the dynamic
processes and movement of organelles in the nerve cells.
Neurite extension and branching are important neuronal plasticity mechanisms that can
lead to the addition of synaptic contacts in developing neurons and changes in the number of
synapses in mature neurons. CaMKII regulates the movement, extension, and branching of
filopodia and fine dendrites as well as the number of synapses in hippocampal neurons. Only
β
CaMKII, not
α
CaMKII, has this morphogenic activity (Fink et al., 2003). CaMKII is
capable of bundling F-actin through a stoichiometric interaction (Shen et al., 1998). In
organotypic slice cultures of the hippocampus, RNAi-mediated down-regulation of CaMKII
leads to a reduction in the volume of dendritic spine heads that is mediated by F-actin
dynamics. This activity was associated with
β
CaMKII in a manner requiring its actin-
binding and association domains, indicating that this feature of CaMKII is necessary for
maintaining the dendritic spine structure (Okamoto et al., 2007).Thus, CaMKII serves as a
central signaling molecule in structural changes during synaptic plasticity.
5-2. Regulation of PSD protein by CaMKII
5-2-1. Molecular constituents of PSD
Important mechanisms for synaptic regulation, including LTP and LTD, may be based on
the PSD (see review; Kennedy, 1997; Kennedy, 2000; Yamauchi, 2002; Sheng &
Hoogenraad, 2007). The PSD is a tiny, amorphous structure located on and beneath the post-
synaptic membrane and is visible under the electron microscope as tight complexes of post-
synaptic junctional proteins. It is a disc-shaped subcellular organelle about 50 nm thick and
100-900 nm in diameter apposed to postsynaptic membranes. Many attempts have been made
to identify and characterize the molecular constituents of the PSD, but, not all constituents are
known (Yamauchi, 2002). Recently, molecular constituents have been analyzed using an
integrated liquid chromatography-based protein identification system, and results provide a
catalogue of the major protein sets associated with the PSD (Yoshimura et al., 2004).
Hundreds of different proteins have been identified in the PSD. The PSD contains various
proteins involved in signal transduction, including receptors, ion channel proteins, protein
kinases and phosphatases, G-protein and related proteins, scaffold proteins, and adaptor
proteins. Structural proteins, including membrane proteins involved in cell adhesion and cell-
cell-interaction, proteins involved in endocytosis, motor proteins, and cytoskeletal proteins
are also abundant.Similar results were reported somewhat later (Yoshimura et al., 2004; Peng
et al., 2004; Sheng & Hoogenraad, 2007).
CaMKII is one of the major proteins in the PSD of the cerebral cortex and hippocampus
(Kennedy et al., 1983; Goldenring et al., 1984; Kelly et al., 1984). Quantitative
immunoblotting combined with scanning transmission electroscopy for estimation of the PSD
mass revealed the CaMKII content per single PSD to be 80 holoenzymes, corresponding to
6% of the total PSD mass (Chen et al., 2005).
Many proteins in the PSD are phosphorylated and regulated by various protein kinases.
