Regulation of CBP-mediated transcription by neuronal calcium signaling.
The transcription factor CREB is involved in mediating many of the long-term effects of activity-dependent plasticity at glutamatergic synapses. Here, we show that activation of NMDA receptors and voltage-sensitive calcium channels leads to CREB-mediated transcription in cortical neurons via a mechanism regulated by CREB-binding protein (CBP). Recruitment of CBP to the promoter is not sufficient for transactivation, but calcium influx can induce CBP-mediated transcription via two distinct transactivation domains. CBP-mediated transcription is stimulus strength-dependent and can be induced by activation of CaM kinase II, CaM kinase IV, and protein kinase A, but not by activation of the Ras-MAP kinase pathway. These observations indicate that CBP can function as a calcium-sensitive transcriptional coactivator that may act as a regulatory switch for glutamate-induced CREB-mediated transcription.
Hu
S C
SC
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Chrivia
J
J
Ghosh
A
A
D000818:Animals; D050882:CREB-Binding Protein; D002118:Calcium / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics*; D010766:Phosphorylation; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D011999:Recruitment, Neurophysiological; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic
D009687:Nuclear Proteins; D015534:Trans-Activators; D018698:Glutamic Acid; D011189:Potassium Chloride; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium