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The COP9 signalosome converts temporal hormone signaling to spatial restriction on neural competence.

Huang YC, Lu YN, Wu JT, Chien CT, Pi H - PLoS Genet. (2014)

Bottom Line: We found that the COP9 signalosome (CSN) suppresses the neural competence of non-innervated bristles at the PWM.Several CSN subunits physically associate with ecdysone receptors to represses br at the transcriptional level.We propose a model in which nuclear hormone receptors cooperate with the deneddylation machinery to temporally shutdown downstream target gene expression, conferring a spatial restriction on neural competence at the PWM.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Insitute of Molecular Biology, Academia Sinica, Taipei, Taiwan.

ABSTRACT
During development, neural competence is conferred and maintained by integrating spatial and temporal regulations. The Drosophila sensory bristles that detect mechanical and chemical stimulations are arranged in stereotypical positions. The anterior wing margin (AWM) is arrayed with neuron-innervated sensory bristles, while posterior wing margin (PWM) bristles are non-innervated. We found that the COP9 signalosome (CSN) suppresses the neural competence of non-innervated bristles at the PWM. In CSN mutants, PWM bristles are transformed into neuron-innervated, which is attributed to sustained expression of the neural-determining factor Senseless (Sens). The CSN suppresses Sens through repression of the ecdysone signaling target gene broad (br) that encodes the BR-Z1 transcription factor to activate sens expression. Strikingly, CSN suppression of BR-Z1 is initiated at the prepupa-to-pupa transition, leading to Sens downregulation, and termination of the neural competence of PWM bristles. The role of ecdysone signaling to repress br after the prepupa-to-pupa transition is distinct from its conventional role in activation, and requires CSN deneddylating activity and multiple cullins, the major substrates of deneddylation. Several CSN subunits physically associate with ecdysone receptors to represses br at the transcriptional level. We propose a model in which nuclear hormone receptors cooperate with the deneddylation machinery to temporally shutdown downstream target gene expression, conferring a spatial restriction on neural competence at the PWM.

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Deneddylation/neddylation and multiple cullins suppress BR-Z1 and Sens expressions at the PWM.(A–H″) 20–24 h APF wing discs. (A–D′) Upregulation of Sens (red in A–B′) and BR-Z1 (red in C–D′) in PWM CSN5 clones were suppressed by wild-type CSN5 (A, A′, C, C′), but not deneddylation-defective CSN5D148N (B, B′, D, D′). (E–H) Upregulation of BR-Z1 (blue) and Sens (red) were observed in  clones of Nedd8AN015 (E), Cu11EX (F), Cul3C7 (G) and Cul4JJ11 (H) at the PWM 20–24 h APF, with a single channel for BR-Z1 (E′–H′) and Sens (E″–H″).
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pgen-1004760-g008: Deneddylation/neddylation and multiple cullins suppress BR-Z1 and Sens expressions at the PWM.(A–H″) 20–24 h APF wing discs. (A–D′) Upregulation of Sens (red in A–B′) and BR-Z1 (red in C–D′) in PWM CSN5 clones were suppressed by wild-type CSN5 (A, A′, C, C′), but not deneddylation-defective CSN5D148N (B, B′, D, D′). (E–H) Upregulation of BR-Z1 (blue) and Sens (red) were observed in clones of Nedd8AN015 (E), Cu11EX (F), Cul3C7 (G) and Cul4JJ11 (H) at the PWM 20–24 h APF, with a single channel for BR-Z1 (E′–H′) and Sens (E″–H″).

Mentions: Deneddylation is coupled with neddylation to cycle cullins between two neddylation states for optimal CRL activities [52]. We first addressed whether the deneddylating activity of the CSN is required to repress BR-Z1 and Sens. Elevated BR-Z1 and Sens expressions in CSN5 cells were completely suppressed by the wild-type CSN5 transgene driven by MS1096-GAL4 in wing discs (Figure 8A, 8A′ 8C, 8C′). However, expression of the deneddylation-defective CSN5D148N mutant [26] failed to decrease BR-Z1 and Sens levels in CSN5 clones (Figure 8B, 8B′, 8D, 8D′). This result suggests the Nedd8 conjugation is involved in BR-Z1 and Sens regulations. Indeed, Nedd8AN015 mutant clones located at the PWM of pupal wings also exhibited BR-Z1 and Sens upregulations (Figure 8E–E″).


The COP9 signalosome converts temporal hormone signaling to spatial restriction on neural competence.

Huang YC, Lu YN, Wu JT, Chien CT, Pi H - PLoS Genet. (2014)

Deneddylation/neddylation and multiple cullins suppress BR-Z1 and Sens expressions at the PWM.(A–H″) 20–24 h APF wing discs. (A–D′) Upregulation of Sens (red in A–B′) and BR-Z1 (red in C–D′) in PWM CSN5 clones were suppressed by wild-type CSN5 (A, A′, C, C′), but not deneddylation-defective CSN5D148N (B, B′, D, D′). (E–H) Upregulation of BR-Z1 (blue) and Sens (red) were observed in  clones of Nedd8AN015 (E), Cu11EX (F), Cul3C7 (G) and Cul4JJ11 (H) at the PWM 20–24 h APF, with a single channel for BR-Z1 (E′–H′) and Sens (E″–H″).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230841&req=5

pgen-1004760-g008: Deneddylation/neddylation and multiple cullins suppress BR-Z1 and Sens expressions at the PWM.(A–H″) 20–24 h APF wing discs. (A–D′) Upregulation of Sens (red in A–B′) and BR-Z1 (red in C–D′) in PWM CSN5 clones were suppressed by wild-type CSN5 (A, A′, C, C′), but not deneddylation-defective CSN5D148N (B, B′, D, D′). (E–H) Upregulation of BR-Z1 (blue) and Sens (red) were observed in clones of Nedd8AN015 (E), Cu11EX (F), Cul3C7 (G) and Cul4JJ11 (H) at the PWM 20–24 h APF, with a single channel for BR-Z1 (E′–H′) and Sens (E″–H″).
Mentions: Deneddylation is coupled with neddylation to cycle cullins between two neddylation states for optimal CRL activities [52]. We first addressed whether the deneddylating activity of the CSN is required to repress BR-Z1 and Sens. Elevated BR-Z1 and Sens expressions in CSN5 cells were completely suppressed by the wild-type CSN5 transgene driven by MS1096-GAL4 in wing discs (Figure 8A, 8A′ 8C, 8C′). However, expression of the deneddylation-defective CSN5D148N mutant [26] failed to decrease BR-Z1 and Sens levels in CSN5 clones (Figure 8B, 8B′, 8D, 8D′). This result suggests the Nedd8 conjugation is involved in BR-Z1 and Sens regulations. Indeed, Nedd8AN015 mutant clones located at the PWM of pupal wings also exhibited BR-Z1 and Sens upregulations (Figure 8E–E″).

Bottom Line: We found that the COP9 signalosome (CSN) suppresses the neural competence of non-innervated bristles at the PWM.Several CSN subunits physically associate with ecdysone receptors to represses br at the transcriptional level.We propose a model in which nuclear hormone receptors cooperate with the deneddylation machinery to temporally shutdown downstream target gene expression, conferring a spatial restriction on neural competence at the PWM.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Insitute of Molecular Biology, Academia Sinica, Taipei, Taiwan.

ABSTRACT
During development, neural competence is conferred and maintained by integrating spatial and temporal regulations. The Drosophila sensory bristles that detect mechanical and chemical stimulations are arranged in stereotypical positions. The anterior wing margin (AWM) is arrayed with neuron-innervated sensory bristles, while posterior wing margin (PWM) bristles are non-innervated. We found that the COP9 signalosome (CSN) suppresses the neural competence of non-innervated bristles at the PWM. In CSN mutants, PWM bristles are transformed into neuron-innervated, which is attributed to sustained expression of the neural-determining factor Senseless (Sens). The CSN suppresses Sens through repression of the ecdysone signaling target gene broad (br) that encodes the BR-Z1 transcription factor to activate sens expression. Strikingly, CSN suppression of BR-Z1 is initiated at the prepupa-to-pupa transition, leading to Sens downregulation, and termination of the neural competence of PWM bristles. The role of ecdysone signaling to repress br after the prepupa-to-pupa transition is distinct from its conventional role in activation, and requires CSN deneddylating activity and multiple cullins, the major substrates of deneddylation. Several CSN subunits physically associate with ecdysone receptors to represses br at the transcriptional level. We propose a model in which nuclear hormone receptors cooperate with the deneddylation machinery to temporally shutdown downstream target gene expression, conferring a spatial restriction on neural competence at the PWM.

Show MeSH
Related in: MedlinePlus