Microtubules are required for NF-κB nuclear translocation in neuroblastoma IMR-32 cells: Modulation by zinc

Gerardo Mackenzie, Carl L Keen, Patricia I. Oteiza

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

The relevance of a functional cytoskeleton for Nuclear Factor-κB (NF-κB) 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 α-p50 that is required for neuronal retrograde and nuclear NF-κB transport. Cells treated with vinblastine, colchicine or cytochalasin D, and zinc deficient cells, all showed a low nuclear NF-κB binding activity, and low nuclear concentrations of RelA and p50. The altered nuclear translocation was reflected by a decreased transactivation of NF-κB-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-κB 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-κB nuclear translocation and subsequent impairment of NF-κB-dependent gene regulation.

Original languageEnglish (US)
Pages (from-to)402-415
Number of pages14
JournalJournal of Neurochemistry
Volume99
Issue number2
DOIs
StatePublished - Oct 2006

Keywords

  • Karyopherin α
  • Microtubules
  • Nervous system
  • NF-κB
  • Nuclear transport
  • Zinc deficiency

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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