Mackenzie Gerardo G, Keen Carl L, Oteiza Patricia I
Department of Nutrition, University of California, Davis, 95616, USA.
J Neurochem. 2006 Oct;99(2):402-15. doi: 10.1111/j.1471-4159.2006.04005.x.
The relevance of a functional cytoskeleton for Nuclear Factor-kappaB (NF-kappaB) nuclear translocation was investigated in neuronal cells, using conditions that led to a disruption of the cytoskeleton [inhibition of tubulin (vinblastine, colchicine), or actin (cytochalasin D) polymerization and zinc deficiency]. We present evidence that an impairment in tubulin polymerization can inhibit the formation of the complex tubulin-dynein-karyopherin alpha-p50 that is required for neuronal retrograde and nuclear NF-kappaB transport. Cells treated with vinblastine, colchicine or cytochalasin D, and zinc deficient cells, all showed a low nuclear NF-kappaB binding activity, and low nuclear concentrations of RelA and p50. The altered nuclear translocation was reflected by a decreased transactivation of NF-kappaB-driven genes. The immunocytochemical characterization of cellular RelA showed that cytoskeleton disruption can lead to an altered distribution of RelA resulting in the formation of peripheral accumuli. These results support the concept that cytoskeleton integrity is necessary for the transport and translocation of NF-kappaB required for synapse to nuclei communication. We suggest that during development, as well as in the adult brain, conditions such as zinc deficiency, that affect the normal structure and function of the cytoskeleton can affect neuronal proliferation, differentiation, and survival by altering NF-kappaB nuclear translocation and subsequent impairment of NF-kappaB-dependent gene regulation.
利用导致细胞骨架破坏的条件（抑制微管蛋白聚合，如长春花碱、秋水仙碱，或肌动蛋白聚合，如细胞松弛素D，以及锌缺乏），在神经元细胞中研究了功能性细胞骨架与核因子-κB（NF-κB）核转位的相关性。我们提供的证据表明，微管蛋白聚合受损可抑制神经元逆行和核NF-κB转运所需的微管蛋白-动力蛋白-核转运蛋白α-p50复合物的形成。用长春花碱、秋水仙碱或细胞松弛素D处理的细胞以及缺锌细胞，均表现出低核NF-κB结合活性，以及RelA和p50的低核浓度。核转位改变表现为NF-κB驱动基因的反式激活减少。细胞RelA的免疫细胞化学特征表明，细胞骨架破坏可导致RelA分布改变，从而形成外周聚集物。这些结果支持了这样一种观点，即细胞骨架完整性对于突触到细胞核通讯所需的NF-κB的转运和转位是必要的。我们认为，在发育过程中以及成人大脑中，诸如锌缺乏等影响细胞骨架正常结构和功能的状况，可通过改变NF-κB核转位以及随后损害NF-κB依赖性基因调控，来影响神经元的增殖、分化和存活。
