regulation of retinoid receptors by retinoic acid and axonal contact in schwann cells类维生素a的监管由视黄酸受体在雪旺细胞和轴突接触.pdfVIP

Regulation of Retinoid Receptors by Retinoic Acid and Axonal Contact in Schwann Cells Maria-Jesus Latasa, Jose Miguel Cosgaya* ´ ´ Department of Endocrine and Nervous System Physiopathology, Instituto de Investigaciones Biomedicas, Consejo Superior de Investigaciones Cientıficas, Universidad ´ Autonoma de Madrid, Madrid, Spain Abstract Background: Schwann cells (SCs) are the cell type responsible for the formation of the myelin sheath in the peripheral nervous system (PNS). As retinoic acid (RA) and other retinoids have a profound effect as regulators of the myelination program, we sought to investigate how their nuclear receptors levels were regulated in this cell type. Methodology/Principal Findings: In the present study, by using Schwann cells primary cultures from neonatal Wistar rat pups, as well as myelinating cocultures of Schwann cells with embryonic rat dorsal root ganglion sensory neurons, we have found that sustained expression of RXR-c depends on the continuous presence of a labile activator, while axonal contact mimickers produced an increase in RXR-c mRNA and protein levels, increment that could be prevented by RA. The upregulation by axonal contact mimickers and the transcriptional downregulation by RA were dependent on de novo protein synthesis and did not involve changes in mRNA stability. On the other hand, RAR-b mRNA levels were only slightly modulated by axonal contact mimickers, while RA produced a strong transcriptional upregulation that was independent of de novo protein synthesis without change