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FoxO limits microtubule stability and is itself negatively regulated by microtubule disruption.

Nechipurenko IV, Broihier HT - J. Cell Biol. (2012)

Bottom Line: Indeed, levels of neuronal FoxO were strongly reduced after acute pharmacological MT disruption as well as sustained genetic disruption of the neuronal cytoskeleton.This decrease was independent of the dual leucine zipper kinase-Wallenda pathway and required function of Akt kinase.We present a model wherein FoxO degradation is a component of a stabilizing, protective response to cytoskeletal insult.

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Affiliation: Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44106, USA.

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FoxO is enriched in a subset of motor neuron nuclei. (A and B) Late-stage wild-type (WT; A) and FoxO GOF (B) embryos stained for Fasciclin 2. (C) Gene structure of Drosophila foxO. Closed rectangles represent exons. The P element (GS1664) used to generate the foxOΔ2 allele and the extent of deletion in the foxOΔ2 mutant are indicated. (D) FoxO protein diagram depicting its major motifs. The positions of the foxO21 and foxO25 mutations are marked above, and the epitope for anti-FoxO is indicated below the diagram. (E) Immunoblot showing FoxO expression in wild-type and foxO alleles. Molecular masses are given in kilodaltons. (F and G) Representative confocal images showing three abdominal segments of the late-stage embryonic (F) and L3 (G) VNC stained for FoxO. (H and I) Higher magnification of partial z stacks through the VNCs of the indicated genotypes. Arrows mark cytoplasmic FoxO. (J and K) Same samples as in F and G, respectively, colabeled with anti-FoxO and anti-pMad. (L) VNC of L3 larva labeled with anti-FoxO showing FoxO knockdown in motor neurons via RNAi. Anterior is up. Bars, 20 µm. OR, Oregon R.
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fig1: FoxO is enriched in a subset of motor neuron nuclei. (A and B) Late-stage wild-type (WT; A) and FoxO GOF (B) embryos stained for Fasciclin 2. (C) Gene structure of Drosophila foxO. Closed rectangles represent exons. The P element (GS1664) used to generate the foxOΔ2 allele and the extent of deletion in the foxOΔ2 mutant are indicated. (D) FoxO protein diagram depicting its major motifs. The positions of the foxO21 and foxO25 mutations are marked above, and the epitope for anti-FoxO is indicated below the diagram. (E) Immunoblot showing FoxO expression in wild-type and foxO alleles. Molecular masses are given in kilodaltons. (F and G) Representative confocal images showing three abdominal segments of the late-stage embryonic (F) and L3 (G) VNC stained for FoxO. (H and I) Higher magnification of partial z stacks through the VNCs of the indicated genotypes. Arrows mark cytoplasmic FoxO. (J and K) Same samples as in F and G, respectively, colabeled with anti-FoxO and anti-pMad. (L) VNC of L3 larva labeled with anti-FoxO showing FoxO knockdown in motor neurons via RNAi. Anterior is up. Bars, 20 µm. OR, Oregon R.

Mentions: foxO was identified in a misexpression screen for genes involved in motor neuron differentiation. An upstream activation sequence (UAS)–containing P element, GS1664, inserted upstream of the foxO gene, disrupts the embryonic axonal scaffold when crossed to the panneuronal driver ElavGal4 (Fig. 1 C and not depicted). The phenotype is attributable to elevated FoxO levels, as ElavGal4-driven overexpression of a UAS-foxOWT transgene yields an equivalent phenotype (Fig. 1, A and B).


FoxO limits microtubule stability and is itself negatively regulated by microtubule disruption.

Nechipurenko IV, Broihier HT - J. Cell Biol. (2012)

FoxO is enriched in a subset of motor neuron nuclei. (A and B) Late-stage wild-type (WT; A) and FoxO GOF (B) embryos stained for Fasciclin 2. (C) Gene structure of Drosophila foxO. Closed rectangles represent exons. The P element (GS1664) used to generate the foxOΔ2 allele and the extent of deletion in the foxOΔ2 mutant are indicated. (D) FoxO protein diagram depicting its major motifs. The positions of the foxO21 and foxO25 mutations are marked above, and the epitope for anti-FoxO is indicated below the diagram. (E) Immunoblot showing FoxO expression in wild-type and foxO alleles. Molecular masses are given in kilodaltons. (F and G) Representative confocal images showing three abdominal segments of the late-stage embryonic (F) and L3 (G) VNC stained for FoxO. (H and I) Higher magnification of partial z stacks through the VNCs of the indicated genotypes. Arrows mark cytoplasmic FoxO. (J and K) Same samples as in F and G, respectively, colabeled with anti-FoxO and anti-pMad. (L) VNC of L3 larva labeled with anti-FoxO showing FoxO knockdown in motor neurons via RNAi. Anterior is up. Bars, 20 µm. OR, Oregon R.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3275378&req=5

fig1: FoxO is enriched in a subset of motor neuron nuclei. (A and B) Late-stage wild-type (WT; A) and FoxO GOF (B) embryos stained for Fasciclin 2. (C) Gene structure of Drosophila foxO. Closed rectangles represent exons. The P element (GS1664) used to generate the foxOΔ2 allele and the extent of deletion in the foxOΔ2 mutant are indicated. (D) FoxO protein diagram depicting its major motifs. The positions of the foxO21 and foxO25 mutations are marked above, and the epitope for anti-FoxO is indicated below the diagram. (E) Immunoblot showing FoxO expression in wild-type and foxO alleles. Molecular masses are given in kilodaltons. (F and G) Representative confocal images showing three abdominal segments of the late-stage embryonic (F) and L3 (G) VNC stained for FoxO. (H and I) Higher magnification of partial z stacks through the VNCs of the indicated genotypes. Arrows mark cytoplasmic FoxO. (J and K) Same samples as in F and G, respectively, colabeled with anti-FoxO and anti-pMad. (L) VNC of L3 larva labeled with anti-FoxO showing FoxO knockdown in motor neurons via RNAi. Anterior is up. Bars, 20 µm. OR, Oregon R.
Mentions: foxO was identified in a misexpression screen for genes involved in motor neuron differentiation. An upstream activation sequence (UAS)–containing P element, GS1664, inserted upstream of the foxO gene, disrupts the embryonic axonal scaffold when crossed to the panneuronal driver ElavGal4 (Fig. 1 C and not depicted). The phenotype is attributable to elevated FoxO levels, as ElavGal4-driven overexpression of a UAS-foxOWT transgene yields an equivalent phenotype (Fig. 1, A and B).

Bottom Line: Indeed, levels of neuronal FoxO were strongly reduced after acute pharmacological MT disruption as well as sustained genetic disruption of the neuronal cytoskeleton.This decrease was independent of the dual leucine zipper kinase-Wallenda pathway and required function of Akt kinase.We present a model wherein FoxO degradation is a component of a stabilizing, protective response to cytoskeletal insult.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44106, USA.

Show MeSH
Related in: MedlinePlus