Age-dependent differences in glutamate-induced phosphorylation systems in rat hippocampal slices.
Glutamate receptor induced changes in the activity of different phosphorylation systems were measured in hippocampal slices from 12- and 56-day-old rats, by determining the endogenous phosphorylation of 2.5% perchloric acid (PCA) soluble proteins. We identified among these proteins an 85, 80 kDa and the tau protein as specific substrates for protein kinase A (PKA), MARCKS, and neurogranin as specific substrates for protein kinase C (PKC), and prostaglandin-D-synthase as substrate for casein kinase II (CKII). In addition, a 35 kDa protein was phosphorylated by calcium/calmodulin dependent kinase II and protein kinase C and a 21 kDa protein was a substrate for all investigated kinases. The basal endogenous phosphorylation of 2.5% PCA soluble proteins changed during development qualitatively and quantitatively. Thus, the phosphorylation degree of nearly all proteins declines during maturation. Activation of mGluR induced an increased phosphorylation of PKA, PKC, and CKII substrates in hippocampal slices from 12-day-old rats, but in slices of 56-day-old rats only PKA and to a lower extent PKC substrates were affected. In contrast, stimulation of NMDA receptors led to an enhancement of CKII and PKA dependent phosphorylation only in slices of young animals, whereas the endogenous phosphorylation of some proteins in adult slices was actually decreased. These data showing developmental changes in the coupling of metabotropic and ionotropic glutamate receptors to different phosphorylation systems are discussed in the light of altered physiological properties of the mature hippocampus.
Angenstein
F
F
Federal Institute for Neurobiology Magdeburg, Germany. angenste@staff.uiuc.edu
Buchner
K
K
Staak
S
S
D000375:Aging / Q000502:physiology*; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000032:analysis / Q000378:metabolism; D047390:Casein Kinase II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000032:analysis / Q000378:metabolism; D034281:Dynamins; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000032:analysis / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D019746:Intramolecular Oxidoreductases / Q000032:analysis / Q000378:metabolism; D054834:Lipocalins; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism; D051579:Neurogranin; D009924:Organ Culture Techniques; D010472:Perchlorates; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000032:analysis / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D012995:Solubility; D013347:Subcellular Fractions / Q000737:chemistry / Q000201:enzymology; D016875:tau Proteins / Q000032:analysis / Q000378:metabolism; D000099291:Adducins
D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002148:Calmodulin-Binding Proteins; D047390:Casein Kinase II; D017868:Cyclic AMP-Dependent Protein Kinases; D034281:Dynamins; D018690:Excitatory Amino Acid Agonists; D020558:GTP Phosphohydrolases; D018698:Glutamic Acid; D019746:Intramolecular Oxidoreductases; D054834:Lipocalins; D008734:Methoxyhydroxyphenylglycol; D016202:N-Methylaspartate; D009419:Nerve Tissue Proteins; D051579:Neurogranin; D010472:Perchlorates; D010750:Phosphoproteins; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D016875:tau Proteins; D000099291:Adducins; C496651:Nrgn protein, rat; C022466:prostaglandin R2 D-isomerase; C010117:3,4-dihydroxyphenylglycol