CaMKII regulates the depalmitoylation and synaptic removal of the scaffold protein AKAP79/150 to mediate structural long-term depression

摘要: Both long-term potentiation (LTP) and depression (LTD) of excitatory synapse strength require the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) its autonomous activity generated by Thr-286 autophosphorylation. Additionally, LTP LTD are correlated with dendritic spine enlargement shrinkage that accompanied synaptic accumulation or removal, respectively, AMPA-receptor regulatory scaffold A-kinase anchoring (AKAP) 79/150. We show here associated indeed requires AKAP79/150 which in turn CaMKII activity. In contrast to normal substrates, substrate sites within N-terminal polybasic membrane–cytoskeletal targeting domain were phosphorylated more efficiently compared Ca2+/CaM-stimulated This unusual regulation was mediated Ca2+/CaM binding resulting protection from phosphorylation presence Ca2+/CaM, a mechanism favors prolonged, weak stimuli versus brief, strong stimuli. Phosphorylation inhibited association F-actin; it also facilitated removal spines but not required for it. By contrast, LTD-induced depalmitoylation on two Cys residues domain. Notably, such blocked inhibition. These results provide how can mediate only through regulated selection; however, case AKAP79/150, indirect effects palmitoylation important than direct phosphorylation. our first evidence function well-described trafficking regulating shrinkage.