Type I adenylyl cyclase functions as a coincidence detector for control of cyclic AMP response element-mediated transcription

Synergistic regulation of transcription by Ca2+ and isoproterenol

Soren Impey, Gary Wayman, Zhiliang Wu, Daniel R. Storm

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Studies carried out with mammals and invertebrates suggest that Ca2+-sensitive adenylyl cyclases may be important for neuroplasticity. Long-term potentiation in the hippocampus requires increases in intracellular Ca2+ which are accompanied by elevated cyclic AMP (cAMP). Furthermore, activation of cAMP-dependent protein kinase is required for the late stage of long-term potentiation in the CA1 region of the hippocampus, which is also sensitive to inhibitors of transcription. Therefore, some forms of synaptic plasticity may require coordinate regulation of transcription by Ca2+ and cAMP. In this study, we demonstrate that the expression of type I adenylyl cyclase in HEK-293 cells allows Ca2+ to stimulate reporter gene activity mediated through the cAMP response element. Furthermore, simultaneous activation by Ca2+ and isoproterenol caused synergistic stimulation of transcription in HEK-293 cells and cultured neurons. We propose that Ca2+ and neurotransmitter stimulation of type I adenylyl cyclase may play a role in synaptic plasticity by generating optimal cAMP signals for regulation of transcription.

Original languageEnglish (US)
Pages (from-to)8272-8281
Number of pages10
JournalMolecular and Cellular Biology
Volume14
Issue number12
StatePublished - Dec 1994
Externally publishedYes

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Response Elements
Isoproterenol
Cyclic AMP
Neuronal Plasticity
Long-Term Potentiation
HEK293 Cells
Hippocampus
Invertebrates
Cyclic AMP-Dependent Protein Kinases
Reporter Genes
Adenylyl Cyclases
Neurotransmitter Agents
Mammals
Neurons
adenylyl cyclase 1

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

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title = "Type I adenylyl cyclase functions as a coincidence detector for control of cyclic AMP response element-mediated transcription: Synergistic regulation of transcription by Ca2+ and isoproterenol",
abstract = "Studies carried out with mammals and invertebrates suggest that Ca2+-sensitive adenylyl cyclases may be important for neuroplasticity. Long-term potentiation in the hippocampus requires increases in intracellular Ca2+ which are accompanied by elevated cyclic AMP (cAMP). Furthermore, activation of cAMP-dependent protein kinase is required for the late stage of long-term potentiation in the CA1 region of the hippocampus, which is also sensitive to inhibitors of transcription. Therefore, some forms of synaptic plasticity may require coordinate regulation of transcription by Ca2+ and cAMP. In this study, we demonstrate that the expression of type I adenylyl cyclase in HEK-293 cells allows Ca2+ to stimulate reporter gene activity mediated through the cAMP response element. Furthermore, simultaneous activation by Ca2+ and isoproterenol caused synergistic stimulation of transcription in HEK-293 cells and cultured neurons. We propose that Ca2+ and neurotransmitter stimulation of type I adenylyl cyclase may play a role in synaptic plasticity by generating optimal cAMP signals for regulation of transcription.",
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AU - Storm, Daniel R.

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