Bolognani Federico, Tanner Daniel C, Nixon Sayuri, Okano Hirotaka J, Okano Hideyuki, Perrone-Bizzozero Nora I
Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
Neurochem Res. 2007 Dec;32(12):2142-51. doi: 10.1007/s11064-007-9388-8. Epub 2007 Jun 19.
Previous work from our laboratory demonstrated that the RNA-binding protein HuD binds to and stabilizes the GAP-43 mRNA. In this study, we characterized the expression of HuD and GAP-43 mRNA in the hippocampus during two forms of neuronal plasticity. During post-natal development, maximal expression of both molecules was found at P5 and their levels steadily decreased thereafter. At P5, HuD was also present in the subventricular zone, where it co-localized with doublecortin. In the adult hippocampus, the basal levels of HuD and GAP-43 were lower than during development but were significantly increased in the dentate gyrus after seizures. The function of HuD in GAP-43 gene expression was confirmed using HuD-KO mice, in which the GAP-43 mRNA was significantly less stable than in wild type mice. Altogether, these results demonstrate that HuD plays a role in the post-transcriptional control of GAP-43 mRNA in dentate granule cells during developmental and adult plasticity.
我们实验室之前的研究表明,RNA结合蛋白HuD与GAP-43 mRNA结合并使其稳定。在本研究中,我们对两种神经元可塑性形式下海马体中HuD和GAP-43 mRNA的表达进行了表征。在出生后发育过程中,这两种分子的最大表达量在出生后第5天(P5)被发现,此后它们的水平稳步下降。在P5时,HuD也存在于脑室下区,在那里它与双皮质素共定位。在成年海马体中,HuD和GAP-43的基础水平低于发育期间,但在癫痫发作后齿状回中显著增加。使用HuD基因敲除(HuD-KO)小鼠证实了HuD在GAP-43基因表达中的功能,在HuD-KO小鼠中,GAP-43 mRNA的稳定性明显低于野生型小鼠。总之,这些结果表明,在发育和成年可塑性过程中,HuD在齿状颗粒细胞中对GAP-43 mRNA的转录后调控中发挥作用。