Regulation of dopaminergic pathways by retinoids: activation of the D2 receptor promoter by members of the retinoic acid receptor-retinoid X receptor family.
Dopamine is a neuromodulator involved in the control of key physiological functions. Dopamine-dependent signal transduction is activated through the interaction with membrane receptors of the seven-transmembrane domain G protein-coupled family. Among them, dopamine D2 receptor is highly expressed in the striatum and the pituitary gland as well as by mesencephalic dopaminergic neurons. Lack of D2 receptors in mice leads to a locomotor parkinsonian-like phenotype and to pituitary tumors. The D2 receptor promoter has characteristics of a housekeeping gene. However, the restricted expression of this gene to particular neurons and cells points to a strict regulation of its expression by cell-specific transcription factors. We demonstrate here that the D2 receptor promoter contains a functional retinoic acid response element. Furthermore, analysis of retinoic acid receptor-null mice supports our finding and shows that in these animals D2 receptor expression is reduced. This finding assigns to retinoids an important role in the control of gene expression in the central nervous system.
Samad
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TA
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/ULP, Collège de France, BP 163, 67404 Illkirch Cedex, Strasbourg, France.
Krezel
W
W
Chambon
P
P
Borrelli
E
E
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004298:Dopamine / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D047488:Retinoid X Receptors; D012176:Retinoids / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D014157:Transcription Factors / Q000378:metabolism*
D017448:Receptors, Dopamine D2; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors; D004298:Dopamine