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 language | English (US) |
|---|---|
| Pages (from-to) | 402-415 |
| Number of pages | 14 |
| Journal | Journal of Neurochemistry |
| Volume | 99 |
| Issue number | 2 |
| DOIs | |
| State | Published - Oct 2006 |
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Keywords
- Karyopherin α
- Microtubules
- Nervous system
- NF-κB
- Nuclear transport
- Zinc deficiency
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience
Cite this
Microtubules are required for NF-κB nuclear translocation in neuroblastoma IMR-32 cells : Modulation by zinc. / Mackenzie, Gerardo; Keen, Carl L; Oteiza, Patricia I.
In: Journal of Neurochemistry, Vol. 99, No. 2, 10.2006, p. 402-415.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Microtubules are required for NF-κB nuclear translocation in neuroblastoma IMR-32 cells
T2 - Modulation by zinc
AU - Mackenzie, Gerardo
AU - Keen, Carl L
AU - Oteiza, Patricia I.
PY - 2006/10
Y1 - 2006/10
N2 - 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.
AB - 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.
KW - Karyopherin α
KW - Microtubules
KW - Nervous system
KW - NF-κB
KW - Nuclear transport
KW - Zinc deficiency
UR - http://www.scopus.com/inward/record.url?scp=33749165927&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33749165927&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2006.04005.x
DO - 10.1111/j.1471-4159.2006.04005.x
M3 - Article
C2 - 17029595
AN - SCOPUS:33749165927
VL - 99
SP - 402
EP - 415
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 2
ER -