D-Serine/N-methyl-D-aspartate receptor signaling decreases DNA-binding activity of the transcriptional repressor DREAM in Müller glia from the retina.
In the adult retina, N-methyl-D-aspartate (NMDA) neurotoxicity induces Müller cell reactive gliosis which is characterized by changes in gene expression that lead to proliferation and affect retinal physiology. The amino acid D-serine is synthesized in Müller cells and modulates these processes acting as a coagonist of NMDA receptors. We have found that the transcription factor DREAM (downstream regulatory element antagonist modulator), which acts as a transcriptional repressor by binding as a tetramer to regulatory elements located in the promoter region of target genes, is expressed in these cells and that its DNA-binding activity is modulated by NMDA receptor activation. Consistently, immunocytochemical analysis demonstrates that NMDA receptor activation induces changes in the nuclear localization of this transcription factor. DREAM is a pleiotropic transcription factor capable to repress and activate genes involved in several physiological events in different tissues. These results link, for the first time, this transcription factor with NMDA-receptor activation. Given the relevance of glutamatergic transmission in the retina and the remarkable functional plasticity of Müller cells, these findings support the notion that the NMDA receptor-dependent modulation of DREAM activity could play a role in relevant physiological processes ranging from retinal response to injury to differentiation capacity of retinal progenitor cells.
Chavira-Suárez
Erika
E
Departamento de Farmacobiología, Cinvestav Sede Sur, México DF, Mexico.
Ramírez
Mónica
M
Lamas
Mónica
M
D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D051605:Kv Channel-Interacting Proteins / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000235:genetics; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics
D004268:DNA-Binding Proteins; C496760:Kcnip3 protein, rat; D051605:Kv Channel-Interacting Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D012097:Repressor Proteins; D018698:Glutamic Acid; D012694:Serine