title: IP3-dependent intracellular Ca2+ release is required for cAMP-induced c-fos expression in hippocampal neurons.
abstract: Ca(2+) and cAMP are widely used in concert by neurons to relay signals from the synapse to the nucleus, where synaptic activity modulates gene expression required for synaptic plasticity. Neurons utilize different transcriptional regulators to integrate information encoded in the spatiotemporal dynamics and magnitude of Ca(2+) and cAMP signals, including some that are Ca(2+)-responsive, some that are cAMP-responsive and some that detect coincident Ca(2+) and cAMP signals. Because Ca(2+) and cAMP can influence each other's amplitude and spatiotemporal characteristics, we investigated how cAMP acts to regulate gene expression when increases in intracellular Ca(2+) are buffered. We show here that cAMP-mobilizing stimuli are unable to induce expression of the immediate early gene c-fos in hippocampal neurons in the presence of the intracellular Ca(2+) buffer BAPTA-AM. Expression of enzymes that attenuate intracellular IP(3) levels also inhibited cAMP-dependent c-fos induction. Synaptic activity induces c-fos transcription through two cis regulatory DNA elements - the CRE and the SRE. We show here that in response to cAMP both CRE-mediated and SRE-mediated induction of a luciferase reporter gene is attenuated by IP(3) metabolizing enzymes. Furthermore, cAMP-induced nuclear translocation of the CREB coactivator TORC1 was inhibited by depletion of intracellular Ca(2+) stores. Our data indicate that Ca(2+) release from IP(3)-sensitive pools is required for cAMP-induced transcription in hippocampal neurons.
authors: Department of Pharmacology, University of Cambridge, UK.
authors: Wenting
authors: W
authors: Zhang
authors: Asmita
authors: A
authors: Tingare
authors: David Chi-Heng
authors: DC
authors: Ng
authors: Hong W
authors: HW
authors: Johnson
authors: Michael J
authors: MJ
authors: Schell
authors: Rebecca L
authors: RL
authors: Lord
authors: Sangeeta
authors: S
authors: Chawla
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002467:Cell Nucleus; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007294:Inositol / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D027602:Serum Response Element / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002614:Chelating Agents; D046912:Multiprotein Complexes; D016760:Proto-Oncogene Proteins c-fos; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D007294:Inositol; D004533:Egtazic Acid; D000242:Cyclic AMP; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D002118:Calcium