Overexpression of CREB reduces CRE-mediated transcription: behavioral and cellular analyses in transgenic mice.
The CREB transcription factor mediates neuronal plasticity in many systems, but the relationship between CREB levels and CRE-mediated transcription in individual neurons in vivo is unclear. In FVB/N nontransgenic mice, we observed that Purkinje cells showed low basal levels of Ser(133)-phosphorylated CREB protein yet displayed strong CRE-directed transcription. Transgenic mice overexpressing CREB in Purkinje cells and dentate gyrus granule cells showed a decreased CRE-lacZ signal in the same cells, indicating repression of ATF/CREB family function. Dentate region long-term potentiation was not altered by these changes in CREB expression. CREB transgenic mice demonstrated an inability to perform the rotarod task, without signs of overt ataxia. Our results demonstrate that the level of phosphorylated CREB protein is not a reliable indicator of CRE-mediated function. Furthermore, we conclude that CRE-mediated transcription may be linked to only a subset of cerebellum-mediated motor behaviors and may not be universally required for long-lasting synaptic potentiation.
Brodie
Christopher R
CR
Institute of Human Genetics, University of Minnesota, Minneapolis, MN 55455, USA.
Khaliq
Mahmooda
M
Yin
Jerry C P
JC
Brent Clark
H
H
Orr
Harry T
HT
Boland
Linda M
LM
D051696:Activating Transcription Factors; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D017930:Genes, Reporter / Q000235:genetics; D007763:Lac Operon / Q000235:genetics; D017774:Long-Term Potentiation / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009048:Motor Skills / Q000502:physiology; D009473:Neuronal Plasticity / Q000235:genetics; D010766:Phosphorylation; D004856:Postural Balance / Q000502:physiology; D011689:Purkinje Cells / Q000378:metabolism; D020218:Response Elements / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
D051696:Activating Transcription Factors; D001798:Blood Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D014157:Transcription Factors