Activation of TrkA by nerve growth factor upregulates expression of the cholinergic gene locus but attenuates the response to ciliary neurotrophic growth factor

被引:42
作者
Berse, B
Lopez-Coviella, I
Blusztajn, JK
机构
[1] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA
[2] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA
关键词
acetylcholine; choline acetyltransferase; mitogen-activated protein kinase; Stat3; vesicular acetylcholine transporter;
D O I
10.1042/0264-6021:3420301
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:301 / 308
页数:8
相关论文
共 71 条
[1]   NERVE GROWTH-FACTOR EMPLOYS MULTIPLE PATHWAYS TO INDUCE PRIMARY RESPONSE GENES IN PC12 CELLS [J].
BATISTATOU, A ;
VOLONTE, C ;
GREENE, LA .
MOLECULAR BIOLOGY OF THE CELL, 1992, 3 (03) :363-371
[2]   PROMOTER ELEMENTS OF THE RAT CHOLINE-ACETYLTRANSFERASE GENE ALLOWING NERVE GROWTH-FACTOR INDUCIBILITY IN TRANSFECTED PRIMARY CULTURED-CELLS [J].
BEJANIN, S ;
HABERT, E ;
BERRARD, S ;
EDWARDS, JBDM ;
LOEFFLER, JP ;
MALLET, J .
JOURNAL OF NEUROCHEMISTRY, 1992, 58 (04) :1580-1583
[3]  
BEJANIN S, 1994, J BIOL CHEM, V269, P21944
[4]  
BERRARD S, 1995, J NEUROCHEM, V65, P939
[5]   Modulation of cholinergic locus expression by glucocorticoids and retinoic acid is cell-type specific [J].
Berse, B ;
Blusztajn, JK .
FEBS LETTERS, 1997, 410 (2-3) :175-179
[6]   COORDINATED UP-REGULATION OF CHOLINE-ACETYLTRANSFERASE AND VESICULAR ACETYLCHOLINE TRANSPORTER GENE-EXPRESSION BY THE RETINOIC ACID RECEPTOR-ALPHA, CAMP, AND LEUKEMIA INHIBITORY FACTOR CILIARY NEUROTROPHIC FACTOR SIGNALING PATHWAYS IN A MURINE SEPTAL CELL-LINE [J].
BERSE, B ;
BLUSZTAJN, JK .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (38) :22101-22104
[7]  
BLUSZTAJN JK, 1992, J NEUROSCI, V12, P793
[8]  
Blusztjan J. K., 1998, Journal of Physiology Paris, V92, P413, DOI 10.1016/S0928-4257(99)80025-4
[9]   Regulation of gliogenesis in the central nervous system by the JAK-STAT signaling pathway [J].
Bonni, A ;
Sun, Y ;
NadalVicens, M ;
Bhatt, A ;
Frank, DA ;
Rozovsky, I ;
Stahl, N ;
Yancopoulos, GD ;
Greenberg, ME .
SCIENCE, 1997, 278 (5337) :477-483
[10]   GROWTH OF A RAT NEUROBLASTOMA CELL LINE IN SERUM-FREE SUPPLEMENTED MEDIUM [J].
BOTTENSTEIN, JE ;
SATO, GH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1979, 76 (01) :514-517