19. Niwa R, Namiki T, Ito K. . Non-molting glossy/shroud encodes a short-chain dehydrogenase/reductase that functions in the "Black Box" of the ecdysteroid biosynthesis pathway. 2010;137:1991-1999
PDF is primarily considered an important component for regulating circadian rhythms in insects, but here we showed that PDF has a novel function in the stimulation of ecdysone biosynthesis. In many cases, a single hormone has multiple functions regulating many physiological phenomena. Thus, both the regulation of receptor expression in the target tissue and the regulation of hormone release are important for the hormone to only affect the target tissue at the appropriate time. In the case of PTTH, the titer of the hormone in the hemolymph is clearly correlated with the ecdysteroid titer , whereas the gene expression pattern of the PTTH receptor Torso is not . However, the PGs of V4 (a low ecdysone level period) are capable of responding to PTTH stimulus and synthesize ecdysone in vitro. Thus, the effect of PTTH is predominantly regulated by the timing of hormone secretion. By contrast, the gene expression of BNGR-B2 (PDFR) was clearly correlated with the hemolymph ecdysteroid titer (), and the amount of ecdysone synthesized and the increase in intracellular cAMP levels induced by PDF was clearly correlated with the expression level of BNGR-B2 (). Therefore, the effect of PDF can be regulated by the expression level of the receptor and/or the timing of hormone secretion. When these results are examined as a whole, PDF plays important roles in regulating the timing of ecdysone biosynthesis.
Important dates in the history of lipids ..
During PTTH-induced ecdysone biosynthesis, the participation of the mitogen-activated protein kinase (MAPK) and TOR pathways has been reported , . To investigate the difference between the PDF- and the PTTH-induced ecdysone biosynthetic pathways, the phosphorylation status of proteins in the MAPK and TOR pathways was investigated. Phosphorylated extracellular signal-regulated kinase (p-ERK) and phosphorylated 4E-BP (p-4E-BP) were used to evaluate the participation of the MAPK and TOR pathways, respectively. The level of p-ERK was upregulated when the PGs were treated with PTTH but not when the PGs were treated with PDF (). In contrast to p-ERK, the level of p-4E-BP was upregulated by both PDF and PTTH (). Because PI3K-mediated phosphorylation of 4E-BP has been reported during PTTH-induced ecdysone biosynthesis , the effect of a PI3K inhibitor (LY294002) on the phosphorylation of 4E-BP by PDF was investigated. The PI3K inhibitor clearly suppressed the ecdysone biosynthesis and phosphorylation of 4E-BP induced by PDF and PTTH (). Furthermore, a PKA inhibitor suppressed both the PDF- and PTTH-induced phosphorylation of 4E-BP (). These results suggest that the TOR-mediated phosphorylation of 4E-BP is regulated by the PKA-PI3K pathway.
Pigment Dispersing Factor Regulates Ecdysone …
Withanolides are known to have important pharmacologicalproperties (anti-tumor, immunosuppressive) but they are also antimicrobial,insect deterrent or ecdysteroid receptor antagonists.
The regulation of ecdysone synthesis by insulin and …
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.
Ecdysone synthesis is triggered when insulin released fro
Ecdysone synthesis is promoted by a second peptide hormone, PTTH, which activates Halloween gene expression via the Torso receptor followed by Ras and Raf in the PG.