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

Christopher R. Brodie; Mahmooda Khaliq; Jerry C.P. Yin; H. Brent Clark; Harry T. Orr; Linda M. Boland

doi:10.1016/j.mcn.2003.11.008

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

Christopher R. Brodie, Mahmooda Khaliq, Jerry C.P. Yin, H. Brent Clark, Harry T. Orr, Linda M. Boland

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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 Ser¹³³-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.

Original language	English (US)
Pages (from-to)	602-611
Number of pages	10
Journal	Molecular and Cellular Neuroscience
Volume	25
Issue number	4
DOIs	https://doi.org/10.1016/j.mcn.2003.11.008
State	Published - Apr 2004

Bibliographical note

Funding Information:
The mouse CREBα cDNA was a kind gift of Günter Schütz (DKFZ Heidelberg). We thank Robert Ehlenfeldt for embryo injection, Steve Bonner for mouse husbandry, Jill Steidl for help with slice recordings, and Paul Mermelstein for helpful comments on the manuscript. This work was supported by NIH/NINDS grant NS31318 (HTO) and the Minnesota Medical Foundation (LMB). C.R.B. was a Howard Hughes Medical Institute Predoctoral Fellow.

Keywords

CRE
CREB
DG
Dentate gyrus
LTD
LTP
Long-term depression
Long-term potentiation
WT
Wild type
cAMP response element
cAMP response element-binding transcription factor

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10.1016/j.mcn.2003.11.008

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title = "Overexpression of CREB reduces CRE-mediated transcription: Behavioral and cellular analyses in transgenic mice",

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 Ser133-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.",

keywords = "CRE, CREB, DG, Dentate gyrus, LTD, LTP, Long-term depression, Long-term potentiation, WT, Wild type, cAMP response element, cAMP response element-binding transcription factor",

author = "Brodie, {Christopher R.} and Mahmooda Khaliq and Yin, {Jerry C.P.} and Clark, {H. Brent} and Orr, {Harry T.} and Boland, {Linda M.}",

note = "Funding Information: The mouse CREBα cDNA was a kind gift of G{\"u}nter Sch{\"u}tz (DKFZ Heidelberg). We thank Robert Ehlenfeldt for embryo injection, Steve Bonner for mouse husbandry, Jill Steidl for help with slice recordings, and Paul Mermelstein for helpful comments on the manuscript. This work was supported by NIH/NINDS grant NS31318 (HTO) and the Minnesota Medical Foundation (LMB). C.R.B. was a Howard Hughes Medical Institute Predoctoral Fellow.",

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AU - Khaliq, Mahmooda

AU - Yin, Jerry C.P.

AU - Clark, H. Brent

AU - Orr, Harry T.

AU - Boland, Linda M.

N1 - Funding Information: The mouse CREBα cDNA was a kind gift of Günter Schütz (DKFZ Heidelberg). We thank Robert Ehlenfeldt for embryo injection, Steve Bonner for mouse husbandry, Jill Steidl for help with slice recordings, and Paul Mermelstein for helpful comments on the manuscript. This work was supported by NIH/NINDS grant NS31318 (HTO) and the Minnesota Medical Foundation (LMB). C.R.B. was a Howard Hughes Medical Institute Predoctoral Fellow.

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N2 - 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 Ser133-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.

AB - 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 Ser133-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.

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

Abstract

Bibliographical note

Keywords

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