Overexpression of CREB reduces CRE-mediated transcription: behavioral and cellular analyses in transgenic mice

Brodie, C. R., Khaliq, M., Yin, J. C. P., Clark, H. B., Orr, H. T., Boland, L. M. (April 2004) Overexpression of CREB reduces CRE-mediated transcription: behavioral and cellular analyses in transgenic mice. Molecular and Cellular Neuroscience, 25 (4). pp. 602-611. ISSN 1044-7431

Abstract

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. (C) 2004 Elsevier Inc. All rights reserved.

Item Type: Paper
Uncontrolled Keywords: ELEMENT-BINDING PROTEIN element binding protein LONG-TERM-MEMORY long term memory HIPPOCAMPAL SYNAPTIC hippocampal synaptic PLASTICITY plasticity GENE-EXPRESSION gene expression PHOSPHORYLATED CREB phosphorylated COACTIVATOR CBP coactivator PURKINJE-CELLS Purkinje cells LATE-PHASE late phase KINASE-A Kinase A ACTIVATOR activator
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > neural plasticity
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:
Communities: CSHL labs > Brody lab
Depositing User: CSHL Librarian
Date: April 2004
Date Deposited: 09 Feb 2012 18:02
Last Modified: 09 Feb 2012 18:02
URI: https://repository.cshl.edu/id/eprint/22330

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