title: Transient translocation of protein kinase Cgamma in hippocampal long-term potentiation depends on activation of metabotropic glutamate receptors.
abstract: Protein kinase C has been implicated in long-term regulation of cellular functions including induction and maintenance of hippocampal long-term potentiation. In the present study the time-course of long-term potentiation-induced translocation of Ca(2+)-dependent protein kinase C isoenzymes (PKCalpha/beta and PKCgamma) was investigated. Quantitative immunoblot analysis was used to measure translocation of these isoenzymes between cytosolic, membrane-associated and membrane-inserted fraction at 5, 15 and 60 min after induction of long-term potentiation in the dentate gyrus in vivo. To investigate the involvement of metabotropic glutamate receptors in protein kinase C regulation during long-term potentiation induction, additional animals were treated before tetanization with (R,S)-alpha-methyl-4-carboxyphenylglycine, an antagonist of metabotropic glutamate receptors. Brief tetanic stimulation of the perforant path resulted in a 100-150% increase in the population spike amplitude in response to test stimuli 5, 15 or 60 min after stimulation in both untreated and (R,S)-alpha-methyl-4-carboxyphenylglycine-treated animals. Only those rats showing clear potentiation were selected for further biochemical analysis of the potentiated dentate gyrus. Five minutes after high-frequency stimulation the subcellular distribution of all studied protein kinase C isoenzymes was unchanged compared with controls. PKC-gamma translocated into the cytosol 15 min after tetanization and this redistribution was blocked by (R,S)-alpha-methyl-4-carboxyphenylgly-cine pretreatment. By contrast, PKC alpha/beta levels increased in the cytosolic fraction only 60 min after tetanization, but in a (R,S)-alpha-methyl-4-carboxyphenylglycine-independent manner. In an additional set of experiments it was shown that (R,S)-alpha-methyl-4-carboxyphenylglycine alone applied intraventricularly had no effect on the subcellular distribution of the studied isoenzymes. The data suggest that PKCalpha/beta and PKCgamma are activated during different post-tetanic phases and metabotropic glutamate receptor activation might be essential for tetanus-induced translocation of postsynaptic PKCgamma only.
authors.affiliation: Leibniz Institute for Neurobiology, Magdeburg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Angenstein
authors.forename: G
authors.initials: G
authors.lastname: Riedel
authors.forename: K G
authors.initials: KG
authors.lastname: Reyman
authors.forename: S
authors.initials: S
authors.lastname: Staak
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D018891:Dentate Gyrus / Q000737:chemistry* / Q000201:enzymology*; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D013347:Subcellular Fractions / Q000201:enzymology
chemical_list: D001565:Benzoates; D018691:Excitatory Amino Acid Antagonists; D007527:Isoenzymes; D018094:Receptors, Metabotropic Glutamate; C079694:alpha-methyl-4-carboxyphenylglycine; C087857:protein kinase C gamma; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D005998:Glycine