Nerve growth factor (NGF) stimulates the expression of the cholinergic gene locus, which encodes choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT), the proteins necessary for the synthesis and storage of the neurotransmitter acetylcholine (ACh). To determine whether this action of NGF is mediated by the p140TrkA NGF receptor (a member of the Trk tyrosine kinase family) we used a murine basal forebrain cholinergic cell line, SN56, stably transfected with rat trkA cDNA. Treatment of these transfectants with NGF activated mitogen-activated protein kinase and increased cytosolic free calcium concentrations, confirming the reconstitution of TrkA-mediated signalling pathways. The expression of ChAT and VAChT mRNA, as well as ACh content, were coordinately up-regulated by NGF in SN56-trkA transfectants. None of these responses occurred in the parental SN56 cells, which do not express endogenous TrkA, indicating that these actions of NGF required TrkA. We previously reported that ciliary neurotrophic factor (CNTF) upregulates the expression of ChAT and VAChT, as well as ACh production, in SN56 cells. The combined treatment of SN56-trkA cells with CNTF and NGF revealed a complex interaction of these factors in the regulation of cholinergic gene locus expression. At low concentrations of CNTF (< 1 ng/ml), the upregulation of ACh synthesis evoked by these factors was additive. However, at higher concentrations of CNTF (> 1 ng/ml), NGF attenuated the stimulatory effect of CNTF on ChAT and VAChT mRNA and ACh content. This attenuation was not due to interference with early steps of CNTF receptor signalling, as pre-treatment of SN56-trkA cells with NGF did not affect the nuclear translocation of the transcription factor, Stat3, evoked by CNTF.
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September 1999
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Research Article|
August 24 1999
Activation of TrkA by nerve growth factor upregulates expression of the cholinergic gene locus but attenuates the response to ciliary neurotrophic growth factor
Brygida BERSE;
Brygida BERSE
1
*Department of Pathology and Laboratory Medicine, Boston University School of Medicine, 85 East Newton Street, Boston, MA 02118, U.S.A.
1To whom correspondence should be addressed (berse@bu.edu).
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Ignacio LOPEZ-COVIELLA;
Ignacio LOPEZ-COVIELLA
†Department of Psychiatry, Boston University School of Medicine, 85 East Newton Street, Boston, MA 02118, U.S.A.
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J. Krzysztof BLUSZTAJN
J. Krzysztof BLUSZTAJN
*Department of Pathology and Laboratory Medicine, Boston University School of Medicine, 85 East Newton Street, Boston, MA 02118, U.S.A.
†Department of Psychiatry, Boston University School of Medicine, 85 East Newton Street, Boston, MA 02118, U.S.A.
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Publisher: Portland Press Ltd
Received:
March 01 1999
Revision Received:
May 24 1999
Accepted:
June 15 1999
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1999
1999
Biochem J (1999) 342 (2): 301–308.
Article history
Received:
March 01 1999
Revision Received:
May 24 1999
Accepted:
June 15 1999
Citation
Brygida BERSE, Ignacio LOPEZ-COVIELLA, J. Krzysztof BLUSZTAJN; Activation of TrkA by nerve growth factor upregulates expression of the cholinergic gene locus but attenuates the response to ciliary neurotrophic growth factor. Biochem J 1 September 1999; 342 (2): 301–308. doi: https://doi.org/10.1042/bj3420301
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