http://nova.newcastle.edu.au/vital/access/services/Feed ${session.getAttribute("locale")} 5 http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1174 Autophosphorylation of Ca²⁺-calmodulin stimulated protein kinase II (CaMKII) at two sites (Thr286 and Thr305/306) is known to regulate the subcellular location and activity of this enzyme in vivo. CaMKII is also known to be autophosphorylated at Thr253 in vitro but the functional effect of phosphorylation at this site and whether it occurs in vivo, is not known. Using antibodies that specifically recognize CaMKII phosphorylated at Thr253 together with FLAG-tagged wild type and phospho- and dephospho-mimic mutants of α-CaMKII, we have shown that Thr253 phosphorylation has no effect on either the Ca²⁺-calmodulin dependent or autonomous kinase activity of recombinant α-CaMKII in vitro. However, the Thr253Asp phosphomimic mutation increased α-CaMKII binding to subcellular fractions enriched in post-synaptic densities (PSDs). The increase in binding was similar in extent, and additive, to that produced by phosphorylation of Thr286. Thr253 phosphorylation was dynamically regulated in intact hippocampal slices. KCl induced depolarisation increased Thr253 phosphorylation and the phospho-Thr253-CaMKII was specifically recovered in the subcellular fraction enriched in PSDs. These results identify Thr253 as an additional site at which CaMKII is phosphorylated in vivo and suggest that this dynamic phosphorylation may regulate CaMKII function by altering its distribution within the cell. 2010-04-27T06:38:16.050Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:4741 It is convenient to divide the development of synaptic networks into two phases: synapse formation during which synaptic contacts are established, and a subsequent maturation phase during which synaptic circuits are fine tuned and the properties of individual synapses are modified. Understanding the complex factors that control the protracted maturation process in humans is likely to be important for understanding a variety of neurological and psychiatric disorders. Chickens provide an ideal experimental model in which maturation specific changes can be identified and the mechanisms controlling them can be elucidated because the maturation phase is protracted and temporally separated from the formation phase. This paper reviews the knowledge about the biological mechanisms involved in the maturation phase of brain development in chickens and presents some new data. Studies of synaptic physiology suggest that maturation may alter the basal set point for stimulus induced synaptic plasticity. Biochemical and pharmacological studies of N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and metabotropic glutamate receptors (mGluRs) revealed major changes in receptor regulation and the intracellular signalling pathways linked to receptor activation. Not surprisingly, therefore, when immature or mature chickens learn the same behavioural task the learning induced molecular events at the synapse are different. Changes in the features of auditory event related potentials and the basal EEG provide non-invasive techniques for monitoring maturation changes in chicken brain but prepulse inhibition (PPI) is too small and variable in chickens to be useful. Experimentally induced mild late-onset hypothyroidism retards some aspects of brain maturation and may help identify some of the mechanisms controlling maturation. 2010-04-27T05:30:48.331Z ]]>