Spatiotemporal dynamics of CREB phosphorylation: transient versus sustained phosphorylation in the developing striatum.
The cAMP response element-binding protein (CREB) is a plasticity-associated transcription factor that can potentially integrate cAMP and calcium signals at the gene activation level. We tested for convergent Ser-133 phosphorylation of CREB via dopamine D1/D5 receptors and L-type calcium channels in organotypic cultures of neonatal striatum. We found such convergence only transiently. Sustained CREB phosphorylation by D1/D5 receptor and L-type channel agonists was targeted to opposite (striosome and matrix) cellular phenotypes. Subsequent expression of the CRE-containing gene, c-fos, matched the divergent patterns of sustained CREB phosphorylation, and both divergent patterns could be switched by inhibition of phosphatases, including calcineurin. Control of the duration of CREB phosphorylation may be a critical regulator of CRE-mediated gene expression by dopamine and calcium.
Liu
F C
FC
Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, Cambridge 02139, USA.
Graybiel
A M
AM
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D019703:Calcineurin; D015220:Calcium Channels / Q000502:physiology; D002148:Calmodulin-Binding Proteins / Q000502:physiology; D003342:Corpus Striatum / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000502:physiology; D010750:Phosphoproteins; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D015220:Calcium Channels; D002148:Calmodulin-Binding Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D016760:Proto-Oncogene Proteins c-fos; D017447:Receptors, Dopamine D1; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases