Enhanced phosphorylation of the postsynaptic protein kinase C substrate RC3/neurogranin during long-term potentiation.
Long-term potentiation (LTP) is a sustained strengthening of synaptic connections that occurs in the mammalian hippocampus, and is a cellular mechanism likely to contribute to memory formation. One question of current interest is whether the biochemical mechanisms responsible for the maintenance of LTP have a presynaptic or postsynaptic locus. We have determined that the phosphorylation of the postsynaptic protein kinase (PKC) substrate RC3/neurogranin is increased in the maintenance phase of LTP, and that the induction of this effect is dependent on activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. The sustained increase in RC3/neurogranin phosphorylation requires ongoing protein kinase activity, as application of the protein kinase inhibitor H-7 after LTP induction can reverse the increased RC3/neurogranin phosphorylation. Overall, these data are evidence for postsynaptic biochemical changes in the maintenance of LTP. They also implicate RC3/neurogranin as a downstream effector of PKC activity in LTP that could contribute to physiologic expression of LTP.
Chen
S J
SJ
Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
Sweatt
J D
JD
Klann
E
E
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D002147:Calmodulin / Q000494:pharmacology; D002148:Calmodulin-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D004558:Electric Stimulation; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D017774:Long-Term Potentiation; D009419:Nerve Tissue Proteins / Q000302:isolation & purification / Q000378:metabolism*; D051579:Neurogranin; D010764:Phosphorylase Kinase / Q000378:metabolism; D010766:Phosphorylation; D017729:Presynaptic Terminals / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013569:Synapses / Q000502:physiology*
D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D009419:Nerve Tissue Proteins; C496651:Nrgn protein, rat; D016194:Receptors, N-Methyl-D-Aspartate; D051579:Neurogranin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D010764:Phosphorylase Kinase; D011493:Protein Kinase C