151. Microtubules are required for NF-kappaB nuclear translocation in neuroblastoma IMR-32 cells: modulation by zinc.
- Author
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Mackenzie GG, Keen CL, and Oteiza PI
- Subjects
- Actins drug effects, Actins metabolism, Active Transport, Cell Nucleus drug effects, Active Transport, Cell Nucleus physiology, Animals, Animals, Newborn, Cell Line, Tumor, Cell Nucleus ultrastructure, Cells, Cultured, Humans, Microtubules ultrastructure, NF-kappa B p50 Subunit metabolism, Neuroblastoma, Neurons drug effects, Neurons ultrastructure, Presynaptic Terminals metabolism, Protein Binding drug effects, Protein Binding physiology, Protein Synthesis Inhibitors pharmacology, Protein Transport physiology, Rats, Rats, Wistar, Synaptic Transmission physiology, Transcription Factor RelA metabolism, Tubulin drug effects, Tubulin metabolism, Tubulin Modulators pharmacology, Zinc deficiency, Cell Nucleus metabolism, Microtubules metabolism, NF-kappa B metabolism, Neurons metabolism, Zinc metabolism
- Abstract
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.
- Published
- 2006
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