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CREB phosphorylation and dephosphorylation: A Ca2(+)- and stimulus duration-dependent switch for hippocampal gene expression CELL Bito, H., Deisseroth, K., Tsien, R. W. 1996; 87 (7): 1203-1214

Abstract

While changes in gene expression are critical for many brain functions, including long-term memory, little is known about the cellular processes that mediate stimulus-transcription coupling at central synapses. In studying the signaling pathways by which synaptic inputs control the phosphorylation state of cyclic AMP-responsive element binding protein (CREB) and determine expression of CRE-regulated genes, we found two important Ca2+/calmodulin (CaM)-regulated mechanisms in hippocampal neurons: a CaM kinase cascade involving nuclear CaMKIV and a calcineurin-dependent regulation of nuclear protein phosphatase 1 activity. Prolongation of the synaptic input on the time scale of minutes, in part by an activity-induced inactivation of calcineurin, greatly extends the period over which phospho-CREB levels are elevated, thus affecting induction of downstream genes.

View details for Web of Science ID A1996WA54100009

View details for PubMedID 8980227