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Neuronatin mRNA in PC12 cells: downregulation by nerve growth factor
Authors:Rajiv Joseph  Wayne Tsang  Dexian Dou  Kevin Nelson  Klaus Edvardsen
Affiliation:aLaboratory of Molecular Neuroscience, Department of Neurology/K-11, Henry Ford Health Sciences Center, 2799 West Grand Boulevard, Detroit, MI 48202, USA;bLaboratory of Molecular Neuro-Oncology, Department of Neurosurgery, Henry Ford Health Sciences Center, 2799 West Grand Boulevard, Detroit, MI 48202, USA
Abstract:Neuronatin was recently cloned from neonatal rat brain (Biochem. Biophys. Res. Commun., 201 (1994) 1227–1234). In subsequent studies, we noted that neuronatin mRNA was brain-specific and that there were two alternatively spliced forms, α and β (Brain Res., 690 (1995) 92–98). Furthermore, on sequencing the human neuronatin gene, it was determined that the α-form was encoded by three exons, and the β-form was encoded by the first and third exons only (Genomics, 33 (1996) 292–297). The middle exon was spliced out in the β-form. The human neuronatin gene is located in single copy on chromosome 20q11.2-12 (Brain Res., 723 (1996) 8–22). These studies called for an understanding of the function of this gene. Therefore, we studied the expression of neuronatin in PC12 cells, an established model of neuronal growth and differentiation. Neuronatin mRNA expression was found to be abundant in undifferentiated PC12 cells. Treatment with nerve growth factor (NGF), resulting in neuronal differentiation, was associated with a downregulation of neuronatin mRNA expression. Removal of NGF was associated with a return of neuronatin mRNA levels towards baseline. These effects appear to be specific for NGF as they were not seen with transforming growth factor, epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate or dexamethasone. Although, basic fibroblast growth factor also reduced neuronatin mRNA levels, the effect was less pronounced than with NGF. The NGF-induced decrease in neuronatin mRNA occurred even in the presence of protein and RNA syntheses inhibitors. Of the two spliced forms, only the α-form was expressed in PC12 cells. In conclusion, we report the presence of neuronatin mRNA in PC12 cells, and that NGF downregulates its expression. These findings provide a basis for investigating the role of neuronatin in neuronal growth and differentiation.
Keywords:Neuronatin   PC12   Nerve growth factor   Development   Brain
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