RT Journal Article
SR Electronic
T1 Activation of Dopamine D4 Receptors Induces Synaptic Translocation of Ca2+/Calmodulin-Dependent Protein Kinase II in Cultured Prefrontal Cortical Neurons
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 813
OP 822
DO 10.1124/mol.105.018853
VO 69
IS 3
A1 Zhenglin Gu
A1 Qian Jiang
A1 Eunice Y. Yuen
A1 Zhen Yan
YR 2006
UL http://molpharm.aspetjournals.org/content/69/3/813.abstract
AB One of the important targets of dopamine D4 receptors in prefrontal cortex (PFC) is the multifunctional Ca2+/calmodulindependent protein kinase II (CaMKII). In the present study, we investigated the effect of D4 receptor activation on subcellular localization of CaMKII. We found that activation of D4 receptors, but not D2 receptors, induced a rapid translocation of α-CaMKII from cytosol to postsynaptic sites in cultured PFC neurons. Activated CaMKII (Thr286 phospho-CaMKII) was also redistributed to postsynaptic sites after D4 receptor stimulation. The translocation was blocked by inhibiting the phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+ signaling. Point mutation of the calmodulin binding site (Ala302), but not the autophosphorylation site (Thr286), of α-CaMKII prevented the D4-induced CaMKII translocation. Moreover, D4 receptors failed to induce CaMKII translocation in the presence of an actin stabilizer, and D4 activation reduced the binding of CaMKII to F-actin. Concomitant with the synaptic accumulation of α-CaMKII in response to D4 receptor activation, a D4-induced increase in the CaMKII phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor glutamate receptor 1 (GluR1) subunits and the amplitude of AMPA receptor-mediated excitatory postsynaptic currents was also observed. Thus, our results show that D4 receptor activation induces the synaptic translocation of CaMKII through a mechanism involving Ca2+/calmodulin and F-actin, which facilitates the regulation of synaptic targets of CaMKII, such as AMPA receptors.