Fournier A E, McKerracher L
Centre for Research in Neuroscience, Montréal General Hospital Research Institute, QC, Canada.
Biochem Cell Biol. 1995 Sep-Oct;73(9-10):659-64. doi: 10.1139/o95-073.
Microtubules are essential components of the cytoskeleton required for axonal growth. To investigate how changes in tubulin transport and expression may affect axon regeneration, injury in the adult mammalian central nervous system was studied. Axotomized retinal ganglion cells (RGCs) that do not regenerate were compared with RGCs that regenerate their axons when the optic nerve is replaced with a peripheral nerve graft. When RGC axons regenerated through peripheral nerve grafts, the rate of slow transport increased but decreased when no regrowth occurred. To investigate the molecular mechanisms that mediate these responses, alterations in tubulin mRNA levels after injury were examined. Total tubulin mRNA levels fell after injury in the optic nerve but increased in those RGCs that regenerated their axons into a peripheral nerve graft. Further, the expression of four separate beta-tubulin isotypes in injured rat RGCs was characterized. mRNA levels for all four isotypes decreased in RGCs after injury in the optic nerve. How the autoregulation of tubulin expression may contribute to the changes in beta-tubulin isotype expression after injury is discussed.
微管是轴突生长所需细胞骨架的重要组成部分。为了研究微管蛋白运输和表达的变化如何影响轴突再生,对成年哺乳动物中枢神经系统损伤进行了研究。将不能再生的切断轴突的视网膜神经节细胞(RGCs)与当视神经被周围神经移植物替代时能使其轴突再生的RGCs进行比较。当RGC轴突通过周围神经移植物再生时,慢速运输速率增加,但在没有再生时则降低。为了研究介导这些反应的分子机制,检测了损伤后微管蛋白mRNA水平的变化。视神经损伤后总微管蛋白mRNA水平下降,但那些轴突再生进入周围神经移植物的RGCs中微管蛋白mRNA水平升高。此外,还对损伤大鼠RGCs中四种不同的β-微管蛋白亚型的表达进行了表征。视神经损伤后RGCs中所有四种亚型的mRNA水平均下降。本文讨论了微管蛋白表达的自动调节如何导致损伤后β-微管蛋白亚型表达的变化。