Localization of the A kinase anchoring protein AKAP79 in the human hippocampus

The phosphorylation state of the proteins, regulated by phosphatases and ki nases, plays an important role in signal transduction and long-term changes in neuronal excitability. In neurons, cAMP-dependent protein kinase (PKA), protein kinase C (PKC) and calcineurin (CN) are attached to a scaffold pro tein, A kinase anchoring protein (AKAP), thought to anchor these three enzy mes to specific sites of action. However, the localization of AKAP, and the predicted sites of linked phosphatase and kinase activities, are still unk nown at the fine structural level. In the present study, we investigated th e distribution of AKAP79 in the hippocampus from postmortem human brains an d lobectomy samples from patients with intractable epilepsy, using preembed ding immunoperoxidase and immunogold histochemical methods. AKAP79 was foun d in the CA1, presubicular and subicular regions, mostly in pyramidal cell dendrites, whereas pyramidal cells in the CA3, CA2 regions and dentate gran ule cells were negative both in postmortem and in surgical samples. In some epileptic cases, the dentate molecular layer and hilar interneurons also b ecame immunoreactive. At the subcellular level, AKAP79 immunoreactivity was present in postsynaptic profiles near, but not attached to, the postsynapt ic density of asymmetrical (presumed excitatory) synapses. We conclude that the spatial selectivity for the action of certain kinases and phosphatases regulating various ligand- and voltage-gated channels may be ensured by th e selective presence of their anchoring protein, AKAP79, at the majority of glutamatergic synapses in the CAI, but not in the CA2/CA3 regions, suggest ing profound differences in signal transduction and long-term synaptic plas ticity between these regions of the human hippocampus.