Direct relation of long-term synaptic potentiation to phosphorylation of membrane protein F₁, a substrate for membrane protein kinase C

One hour after long-term potentiation (LTP) in the intact hippocampus, a selective increase in protein F₁ in vitro phosphorylation was observed in homogenate prepared from dorsal hippocampus. Protein F₁ phosphorylation was directly related to the magnitude and persistence of potentiation. No other phosphoprotein studied exhibited a relationship with synaptic enhancement. Low-frequency, non-potentiating stimulation did not increase protein F₁ phosphorylation, and phosphorylation of F₁ was not elevated when high-frequency stimulation did not produce potentiation. We also confirmed our earlier demonstration of a similar pattern of results 5 min after LTP. In related work we have previously observed: (1) that protein F₁ is a substrate for protein kinase C (PKC); (2) that membrane PKC activity was increased by translocation from the cytosol following LTP; and (3) that membrane PKC activity was directly related to the persistence of enhancement. We therefore predicted in the present study that protein F₁ phosphorylation in a dorsal hippocampal membrane fraction would be related to LTP. Hippocampal membrane protein F₁ was found to be directly related to both the magnitude and persistence of response enhancement. Thus the molecular events leading to prolonged potentiation may involve increased PKC/protein F₁ association. Persistence of potentiation may be related to synaptic growth processes involving the growth-associated function of protein F₁.