CREB Phosphorylation and Dephosphorylation: A Ca2+- and Stimulus Duration–Dependent Switch for Hippocampal Gene Expression
CellPublished 1 December 1996Open access
Haruhiko Bito, Karl Deisseroth, Richard W. Tsien
Citations1,125
SJR quartileQ1
SJR score22.61
SNIP7.62
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TL;DR
Two important Ca2+/calmodulin (CaM)-regulated mechanisms in hippocampal neurons are found: a CaM kinase cascade involving nuclear CaMKIV and a calcineurin-dependent regulation of nuclear protein phosphatase 1 activity.
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.
Keywords
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