Reference Report

Reference
Citation	Nechipurenko, I.V., Broihier, H.T. (2012). FoxO limits microtubule stability and is itself negatively regulated by microtubule disruption. J. Cell Biol. 196(3): 345--362. (Export to RIS)
FlyBase ID	FBrf0217391
Publication Type	Research paper
PubMed ID	22312004
PubMed 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.
DOI	10.1083/jcb.201105154
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Language of Publication	English
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Publication Type	Journal
Abbreviation	J. Cell Biol.
Title	Journal of Cell Biology
Publication Year	1966-
ISBN/ISSN	0021-9525
Data from Reference
Alleles (30)
	Akt1⁰⁴²²⁶ Akt1^GD1361 Ank2^f02001 bsk^{K53R.Scer\UAS} ckn^{K.Δ324-331.Scer\UAS} cmpy^Δ8 Fmr1^Scer\UAS.cZa foxo²¹ foxo²⁵ foxo^GS1664 foxo^HMS00422 foxo^HMS00793 foxo^KK108590 foxo^Scer\UAS.cFa foxo^Scer\UAS.cTa foxo^TM.Scer\UAS foxo^Δ2 foxo^Δ94 futsch^K68 futsch^N94 kay^Fbz.Scer\UAS Rab3^rup Scer\GAL4^D42 Scer\GAL4^elav.PLu Scer\GAL4^elav-C155 Scer\GAL4^Rapgap1-OK6 wnd¹ wnd² wnd³ α-Spec^GD9695
Constructs (14)
	P{GAL4-elav.L} P{GD1361} P{GD9695} P{GSV1} P{KK108590} P{TRiP.HMS00422} P{TRiP.HMS00793} P{UAS-bsk.K53R} P{UAS-ckn.Δ324-331} P{UAS-Fmr1.Z} P{UAS-foxo.F} P{UAS-foxo.T} P{UAS-foxo.TM} P{UAS-Fra.Fbz}
Genes (18)
	Akt1 Ank2 brp bsk ckn cmpy eve Fas2 Fmr1 foxo futsch HGTX kay Rab3 Scer\GAL4 VGlut wnd α-Spec
Insertions (4)
	P{GawB}D42 P{GawB}elav^C155 P{GawB}OK6 P{GSV1}foxo^GS1664
Natural transposons (1)
	P-element