Failure of Ca2+-activated, CREB-dependent transcription in astrocytes.
Astrocytes participate in signaling via Ca(2+) transients that spread from cell to cell across a multicellular syncytium. The effect, if any, of these Ca(2+) waves on the transcription of Ca(2+)/cAMP-regulatory element binding protein (CREB)-dependent genes is not known. We report here that, unlike neurons, increasing intracellular Ca(2+) in cultured mouse cortical astrocytes failed to activate CREB-dependent transcription, even though CREB was phosphorylated at serine 133. In contrast, both CREB phosphorylation and CREB-dependent transcription were robustly stimulated by increasing cAMP. The failure of Ca(2+)-activated transcription in astrocytes was correlated with the absence of CaMKIV, a Ca(2+)-dependent protein kinase required for Ca(2+)-stimulated gene transcription in neurons. The inability of Ca(2+) to signal via CaMKIV may insulate CREB-dependent gene transcription in astrocytes from activation by Ca(2+) waves.
Murray
Peter D
PD
Department of Physiology, University of Maryland School of Medicine, 655 W. Baltimore St., Baltimore, MD 21201, USA.
Kingsbury
Tami J
TJ
Krueger
Bruce K
BK
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002614:Chelating Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D019319:Okadaic Acid / Q000494:pharmacology; D014162:Transfection / Q000379:methods
D002614:Chelating Agents; D004791:Enzyme Inhibitors; D007476:Ionophores; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D019319:Okadaic Acid; D004533:Egtazic Acid; D015759:Ionomycin; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D050882:CREB-Binding Protein; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; C517685:Camk4 protein, mouse; D002118:Calcium