Microtubules are required for NF-kappaB nuclear translocation in neuroblastoma IMR-32 cells: modulation by zinc.
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.
Mackenzie
Gerardo G
GG
Department of Nutrition, University of California, Davis, 95616, USA.
Keen
Carl L
CL
Oteiza
Patricia I
PI
D000199:Actins / Q000187:drug effects / Q000378:metabolism; D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D006801:Humans; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000502:physiology; D051996:Transcription Factor RelA / Q000378:metabolism; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology; D015032:Zinc / Q000172:deficiency / Q000378:metabolism*
D000199:Actins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D011500:Protein Synthesis Inhibitors; D051996:Transcription Factor RelA; D014404:Tubulin; D050257:Tubulin Modulators; D015032:Zinc