Calcineurin activity is required for depolarization-induced, CREB-dependent gene transcription in cortical neurons.

Calcineurin activity is required for depolarization-induced, CREB-dependent gene transcription in cortical neurons. Research Abstract Details 

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Calcineurin activity is required for depolarization-induced, CREB-dependent gene transcription in cortical neurons. Abstract Text:

Tami J Kingsbury,Linda L Bambrick,Clinton D Roby,Bruce K Krueger,

Cyclic AMP response element binding protein (CREB) functions as an activity-dependent transcription factor in the nervous system. Increases in intracellular Ca(2+) due to neuronal activity lead to the phosphorylation and subsequent activation of CREB. Although phosphorylation of CREB at Ser-133 is necessary for the stimulation of transcriptional activity, it is not sufficient. Here we demonstrate that in mouse cortical neurons, inhibition of the Ca(2+)-dependent protein phosphatase calcineurin by FK506 or cyclosporine A blocks CREB-dependent gene expression induced by depolarization without inhibiting depolarization-induced Ca(2+) influx or CREB Ser-133 phosphorylation. Over-expression of a constitutively-active allele of the transducer of regulated CREB activity could not bypass the requirement for calcineurin activity. Stimulation of a CRE-luciferase reporter gene by depolarization was sensitive to FK506 throughout the entire time course of the transcriptional response, revealing that calcineurin activity is required to maintain CREB-dependent transcription. Stimulation of CRE-luciferase expression by forskolin and 8-Br-cAMP also required calcineurin activity. These results suggest that calcineurin functions as a critical determinant in shaping genome responses to CREB activation in cortical neurons.

Calcineurin activity is required for depolarization-induced, CREB-dependent gene transcription in cortical neurons. Publishing Authors By Initials

TJ Kingsbury,LL Bambrick,CD Roby,BK Krueger,

For similar genetic processes: gene expression: transcription, genetic research abstracts see: genetic processes: gene expression: transcription, genetic research

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Calcineurin activity is required for depolarization-induced, CREB-dependent gene transcription in cortical neurons. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of neurochemistry

VOLUME: 103

Page Numbers: 761-70

Journal Abbreviation: J. Neurochem.

ISSN: 0022-3042

DAY: 31

MONTH: 07

YEAR: 2007

Calcineurin activity is required for depolarization-induced, CREB-dependent gene transcription in cortical neurons. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985190

Calcineurin activity is required for depolarization-induced, CREB-dependent gene transcription in cortical neurons. Keywords Mesh Terms:

KEYWORDS: Transcription, Genetic

MESH TERMS: physiology

Chemical & Substance for Abstract: Calcineurin activity is required for depolarization-induced, CREB-dependent gene transcription in cortical neurons. Information

Substance Name: Calcineurin

Registry Number: EC 3.1.3.-

Grant and Affiliation Information for Calcineurin activity is required for depolarization-induced, CREB-dependent gene transcription in cortical neurons.

AFFILIATION: Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. tking001@umaryland.edu

Country: England

AGENCY: United States NINDS

GRANT: R01NS048095

ACRONYM: NS

MEDLINETA: J Neurochem

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