Activity of the rat GluR4 promoter in transfected cortical neurons and glia

被引:9
作者
Borges, K [1 ]
Myers, SJ [1 ]
Zhang, SN [1 ]
Dingledine, R [1 ]
机构
[1] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA
关键词
astrocyte; GluR1; GluR2; glutamate receptor; GRIA4; neuronal expression;
D O I
10.1046/j.1471-4159.2003.01926.x
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
AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate) receptors are assembled from four subunits, GluR1-4. Although GluR4 is widely expressed in brain its abundance is less than GluR1-3. We have isolated similar to5 kb of the rat GluR4 promoter region and analyzed its capacity to drive expression of a luciferase reporter gene in transfected rat cortical neurons and glia, and C6 glioma cells. Multiple transcriptional start sites were identified in a GC-rich region lacking TATA-boxes between - 1090 and - 1011 bp from ATG. In transfected mixed cortical cultures, luciferase expression driven by GluR4 promoter segments were found predominantly in TuJ1-positive neurons, indicating neuronal preference of GluR4. The GluR4 promoter fragments were 6-12-fold more active in neurons than glia, compared with a 30-fold neuronal selectivity of GluR2. Deletion of the GluR4 transcriptional initiation region decreased luciferase activity in neurons, but increased activity in C6 cells, suggesting that regulatory elements governing neuronal expression reside in this region. An intron within the 5'-untranslated region and Sp1, IK2 and E-box sites are conserved in the rat, mouse and human GluR4 promoters. The relative activity of GluR4 and GluR2 promoters in transfected cells correlates with their expression in brain, and in both promoters regulatory elements for neuronal expression reside near the initiation sites.
引用
收藏
页码:1162 / 1173
页数:12
相关论文
共 41 条
[21]   Changes in GluR4 expression induced by metabotropic receptor activation in radial glia cultures [J].
Löpez, T ;
López-Colomé, AM ;
Ortega, A .
MOLECULAR BRAIN RESEARCH, 1998, 58 (1-2) :40-46
[22]   Heteromeric AMPA receptors assemble with a preferred subunit stoichiometry and spatial arrangement [J].
Mansour, M ;
Nagarajan, N ;
Nehring, RB ;
Clements, JD ;
Rosenmund, C .
NEURON, 2001, 32 (05) :841-853
[23]  
MARTIN LJ, 1993, J NEUROSCI, V13, P2249
[24]   A MOLECULAR DETERMINANT FOR SUBMILLISECOND DESENSITIZATION IN GLUTAMATE RECEPTORS [J].
MOSBACHER, J ;
SCHOEPFER, R ;
MONYER, H ;
BURNASHEV, N ;
SEEBURG, PH ;
RUPPERSBERG, JP .
SCIENCE, 1994, 266 (5187) :1059-1062
[25]  
Myers SJ, 1998, J NEUROSCI, V18, P6723
[26]   Genetic regulation of glutamate receptor ion channels [J].
Myers, SJ ;
Dingledine, R ;
Borges, K .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1999, 39 :221-241
[27]   AMPA-kainate subtypes of glutamate receptor in rat cerebral microglia [J].
Noda, M ;
Nakanishi, H ;
Nabekura, J ;
Akaike, N .
JOURNAL OF NEUROSCIENCE, 2000, 20 (01) :251-258
[28]   Eos and Pegasus, two members of the Ikaros family of proteins with distinct DNA binding activities [J].
Perdomo, J ;
Holmes, M ;
Chong, E ;
Crossley, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (49) :38347-38354
[29]   LIGHT AND ELECTRON IMMUNOCYTOCHEMICAL LOCALIZATION OF AMPA-SELECTIVE GLUTAMATE RECEPTORS IN THE RAT-BRAIN [J].
PETRALIA, RS ;
WENTHOLD, RJ .
JOURNAL OF COMPARATIVE NEUROLOGY, 1992, 318 (03) :329-354
[30]   MatInd and MatInspector: New fast and versatile tools for detection of consensus matches in nucleotide sequence data [J].
Quandt, K ;
Frech, K ;
Karas, H ;
Wingender, E ;
Werner, T .
NUCLEIC ACIDS RESEARCH, 1995, 23 (23) :4878-4884