Ca(2+)-independent autophosphorylation of postsynaptic density-associated Ca2+/calmodulin-dependent protein kinase.

A major protein in the postsynaptic density fraction is alpha-CAM kinase II, the alpha-subunit of the Ca2+/calmodulin-dependent protein kinase. Autophosphorylation of the postsynaptic density-associated CaM kinase II is likely to be a crucial event in the induction of activity-dependent synaptic modification. This study focuses on the regulation and consequences of Ca(2+)-independent autophosphorylation of the enzyme. In isolated postsynaptic densities, a sub-stochiometric level of autophosphorylation in the presence of Ca2+ is sufficient to trigger maximal Ca(2+)-independent autophosphorylation of alpha-CaM Kinase II. A major fraction of the sites phosphorylated in the absence of Ca2+ can be dephosphorylated by the endogenous phosphatase activity in the preparation. Ca(2+)-independent autophosphorylation is correlated with a drastic decrease in calmodulin binding to postsynaptic densities. This may represent a physiological mechanism that lower the calmodulin trapping capacity of the organelle, thus increasing the availability of calmodulin to other elements within a spine.