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PMID:22312004
| Citation |
Nechipurenko, IV and Broihier, HT (2012) FoxO limits microtubule stability and is itself negatively regulated by microtubule disruption. J. Cell Biol. 196:345-62 |
|---|---|
| Abstract |
Transcription factors are essential for regulating neuronal microtubules (MTs) during development and after axon damage. In this paper, we identify a novel neuronal function for Drosophila melanogaster FoxO in limiting MT stability at the neuromuscular junction (NMJ). foxO loss-of-function NMJs displayed augmented MT stability. In contrast, motor neuronal overexpression of wild-type FoxO moderately destabilized MTs, whereas overexpression of constitutively nuclear FoxO severely destabilized MTs. Thus, FoxO negatively regulates synaptic MT stability. FoxO family members are well-established components of stress-activated feedback loops. We hypothesized that FoxO might also be regulated by cytoskeletal stress because it was well situated to shape neuronal MT organization after cytoskeletal damage. 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. |
| Links |
PubMed PMC3275378 Online version:10.1083/jcb.201105154 |
| Keywords |
Animals; Cytoskeleton/metabolism; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster/metabolism; Embryo, Nonmammalian/metabolism; Fluorescent Antibody Technique; Forkhead Transcription Factors/genetics; Forkhead Transcription Factors/metabolism; Microtubules/metabolism; Motor Neurons/metabolism; Mutation |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
involved_in |
GO:0001578: microtubule bundle formation |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
See also
References
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