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Pigment dispersing factor regulates ecdysone biosynthesis via bombyx neuropeptide G protein coupled receptor-B2 in the prothoracic glands of Bombyx mori.

Iga M, Nakaoka T, Suzuki Y, Kataoka H - PLoS ONE (2014)

Bottom Line: Furthermore, we identified PDF as a ligand for BNGR-B2.PDF did not affect the transcript level of known ecdysone biosynthetic enzymes, and inhibiting transcription did not suppress ecdysone biosynthesis, suggesting that the effects of PDF might be mediated by translational regulation and/or post-translational modification.In addition, the participation of protein kinase A (PKA), phosphatidylinositol 3-kinase (PI3K), target of rapamycin (TOR) and eukaryotic translation initiation factor 4E (eIF4E)-binding protein (4E-BP) in the PDF signaling pathway was discovered.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan.

ABSTRACT
Ecdysone is the key hormone regulating insect growth and development. Ecdysone synthesis occurs in the prothoracic glands (PGs) and is regulated by several neuropeptides. Four prothoracicotropic and three prothoracicostatic factors have been identified to date, suggesting that ecdysone biosynthesis is intricately regulated. Here, we demonstrate that the neuropeptide pigment dispersing factor (PDF) stimulates ecdysone biosynthesis and that this novel signaling pathway partially overlaps with the prothoracicotropic hormone (PTTH) signaling pathway. We performed transcriptome analysis and focused on receptors predominantly expressed in the PGs. From this screen, we identified a candidate orphan G protein coupled receptor (GPCR), Bombyx neuropeptide GPCR-B2 (BNGR-B2). BNGR-B2 was predominantly expressed in ecdysteroidogenic tissues, and the expression pattern in the PGs corresponded to the ecdysteroid titer in the hemolymph. Furthermore, we identified PDF as a ligand for BNGR-B2. PDF stimulated ecdysone biosynthesis in the PGs, but the stimulation was only observed in the PGs during a specific larval stage. PDF did not affect the transcript level of known ecdysone biosynthetic enzymes, and inhibiting transcription did not suppress ecdysone biosynthesis, suggesting that the effects of PDF might be mediated by translational regulation and/or post-translational modification. In addition, the participation of protein kinase A (PKA), phosphatidylinositol 3-kinase (PI3K), target of rapamycin (TOR) and eukaryotic translation initiation factor 4E (eIF4E)-binding protein (4E-BP) in the PDF signaling pathway was discovered.

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Integration of the PDF signaling model with the known PTTH signaling pathway.Solid lines indicate demonstrated or highly likely pathways, and dashed lines indicate hypothetical pathways. Gαs: G protein αs subunit, AC: adenylate cyclase, AMP: adenosine monophosphate, cAMP: cyclic AMP, EPAC: exchange protein directly activated by cAMP, eIF4e: eukaryotic translation initiation factor 4E, 4E-BP: eIF4E binding protein, TOR: target of rapamycin, PKA: protein kinase A, PKC: protein kinase C, PI3K: phosphatidylinositol 3-kinase, AKT: protein kinase B, CREB: cAMP response element-binding protein, MAPK: mitogen-activated protein kinase, ERK: extracellular signal-regulated kinase, MEK: MAP kinase kinase, Raf: MAP kinase kinase kinase, S6: ribosomal protein S6, p70S6K: 70 kDa S6 kinase, PLC: phospholipase C, DAG: diacylglycerol, IP3: inositol 1,4,5-trisphosphate, IP3R: IP3 receptor, CaM: calmodulin.
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pone-0103239-g005: Integration of the PDF signaling model with the known PTTH signaling pathway.Solid lines indicate demonstrated or highly likely pathways, and dashed lines indicate hypothetical pathways. Gαs: G protein αs subunit, AC: adenylate cyclase, AMP: adenosine monophosphate, cAMP: cyclic AMP, EPAC: exchange protein directly activated by cAMP, eIF4e: eukaryotic translation initiation factor 4E, 4E-BP: eIF4E binding protein, TOR: target of rapamycin, PKA: protein kinase A, PKC: protein kinase C, PI3K: phosphatidylinositol 3-kinase, AKT: protein kinase B, CREB: cAMP response element-binding protein, MAPK: mitogen-activated protein kinase, ERK: extracellular signal-regulated kinase, MEK: MAP kinase kinase, Raf: MAP kinase kinase kinase, S6: ribosomal protein S6, p70S6K: 70 kDa S6 kinase, PLC: phospholipase C, DAG: diacylglycerol, IP3: inositol 1,4,5-trisphosphate, IP3R: IP3 receptor, CaM: calmodulin.

Mentions: Figure 5 shows the PDF-induced ecdysone biosynthesis signaling model with the known PTTH signaling. PDF binds to BNGR-B2 and upregulates intracellular cAMP levels. cAMP activates PKA, which directly or indirectly affects the PI3K-TOR-4E-BP pathway. Phosphorylated 4E-BP might be released from eIF4e, and translation is initiated. Furthermore, post-translational modification by PKA and/or other kinase(s) might play an important role in regulating ecdysone biosynthesis. In addition to the cAMP-mediated pathway, PDF regulates ecdysone biosynthesis via an extracellular Ca2+-mediated pathway. Thus, PDF regulates ecdysone biosynthesis via two different pathways, partially overlapping with the PTTH signaling pathway. These findings aid in the elucidation of the intricate neuropeptide network regulating ecdysone biosynthesis.


Pigment dispersing factor regulates ecdysone biosynthesis via bombyx neuropeptide G protein coupled receptor-B2 in the prothoracic glands of Bombyx mori.

Iga M, Nakaoka T, Suzuki Y, Kataoka H - PLoS ONE (2014)

Integration of the PDF signaling model with the known PTTH signaling pathway.Solid lines indicate demonstrated or highly likely pathways, and dashed lines indicate hypothetical pathways. Gαs: G protein αs subunit, AC: adenylate cyclase, AMP: adenosine monophosphate, cAMP: cyclic AMP, EPAC: exchange protein directly activated by cAMP, eIF4e: eukaryotic translation initiation factor 4E, 4E-BP: eIF4E binding protein, TOR: target of rapamycin, PKA: protein kinase A, PKC: protein kinase C, PI3K: phosphatidylinositol 3-kinase, AKT: protein kinase B, CREB: cAMP response element-binding protein, MAPK: mitogen-activated protein kinase, ERK: extracellular signal-regulated kinase, MEK: MAP kinase kinase, Raf: MAP kinase kinase kinase, S6: ribosomal protein S6, p70S6K: 70 kDa S6 kinase, PLC: phospholipase C, DAG: diacylglycerol, IP3: inositol 1,4,5-trisphosphate, IP3R: IP3 receptor, CaM: calmodulin.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4114559&req=5

pone-0103239-g005: Integration of the PDF signaling model with the known PTTH signaling pathway.Solid lines indicate demonstrated or highly likely pathways, and dashed lines indicate hypothetical pathways. Gαs: G protein αs subunit, AC: adenylate cyclase, AMP: adenosine monophosphate, cAMP: cyclic AMP, EPAC: exchange protein directly activated by cAMP, eIF4e: eukaryotic translation initiation factor 4E, 4E-BP: eIF4E binding protein, TOR: target of rapamycin, PKA: protein kinase A, PKC: protein kinase C, PI3K: phosphatidylinositol 3-kinase, AKT: protein kinase B, CREB: cAMP response element-binding protein, MAPK: mitogen-activated protein kinase, ERK: extracellular signal-regulated kinase, MEK: MAP kinase kinase, Raf: MAP kinase kinase kinase, S6: ribosomal protein S6, p70S6K: 70 kDa S6 kinase, PLC: phospholipase C, DAG: diacylglycerol, IP3: inositol 1,4,5-trisphosphate, IP3R: IP3 receptor, CaM: calmodulin.
Mentions: Figure 5 shows the PDF-induced ecdysone biosynthesis signaling model with the known PTTH signaling. PDF binds to BNGR-B2 and upregulates intracellular cAMP levels. cAMP activates PKA, which directly or indirectly affects the PI3K-TOR-4E-BP pathway. Phosphorylated 4E-BP might be released from eIF4e, and translation is initiated. Furthermore, post-translational modification by PKA and/or other kinase(s) might play an important role in regulating ecdysone biosynthesis. In addition to the cAMP-mediated pathway, PDF regulates ecdysone biosynthesis via an extracellular Ca2+-mediated pathway. Thus, PDF regulates ecdysone biosynthesis via two different pathways, partially overlapping with the PTTH signaling pathway. These findings aid in the elucidation of the intricate neuropeptide network regulating ecdysone biosynthesis.

Bottom Line: Furthermore, we identified PDF as a ligand for BNGR-B2.PDF did not affect the transcript level of known ecdysone biosynthetic enzymes, and inhibiting transcription did not suppress ecdysone biosynthesis, suggesting that the effects of PDF might be mediated by translational regulation and/or post-translational modification.In addition, the participation of protein kinase A (PKA), phosphatidylinositol 3-kinase (PI3K), target of rapamycin (TOR) and eukaryotic translation initiation factor 4E (eIF4E)-binding protein (4E-BP) in the PDF signaling pathway was discovered.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan.

ABSTRACT
Ecdysone is the key hormone regulating insect growth and development. Ecdysone synthesis occurs in the prothoracic glands (PGs) and is regulated by several neuropeptides. Four prothoracicotropic and three prothoracicostatic factors have been identified to date, suggesting that ecdysone biosynthesis is intricately regulated. Here, we demonstrate that the neuropeptide pigment dispersing factor (PDF) stimulates ecdysone biosynthesis and that this novel signaling pathway partially overlaps with the prothoracicotropic hormone (PTTH) signaling pathway. We performed transcriptome analysis and focused on receptors predominantly expressed in the PGs. From this screen, we identified a candidate orphan G protein coupled receptor (GPCR), Bombyx neuropeptide GPCR-B2 (BNGR-B2). BNGR-B2 was predominantly expressed in ecdysteroidogenic tissues, and the expression pattern in the PGs corresponded to the ecdysteroid titer in the hemolymph. Furthermore, we identified PDF as a ligand for BNGR-B2. PDF stimulated ecdysone biosynthesis in the PGs, but the stimulation was only observed in the PGs during a specific larval stage. PDF did not affect the transcript level of known ecdysone biosynthetic enzymes, and inhibiting transcription did not suppress ecdysone biosynthesis, suggesting that the effects of PDF might be mediated by translational regulation and/or post-translational modification. In addition, the participation of protein kinase A (PKA), phosphatidylinositol 3-kinase (PI3K), target of rapamycin (TOR) and eukaryotic translation initiation factor 4E (eIF4E)-binding protein (4E-BP) in the PDF signaling pathway was discovered.

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