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Article ; Online: A nutrient-responsive hormonal circuit mediates an inter-tissue program regulating metabolic homeostasis in adult Drosophila

Takashi Koyama / Selim Terhzaz / Muhammad T. Naseem / Stanislav Nagy / Kim Rewitz / Julian A. T. Dow / Shireen A. Davies / Kenneth V. Halberg

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 19

Abstract: Maintaining metabolic homeostasis during feeding and fasting states is critical to animal survival. Here the authors show that Capa hormone signaling, homologs to mammalian Neuromedin U, helps control homeostasis via regulation of nutrient uptake and ... ...

Abstract	Maintaining metabolic homeostasis during feeding and fasting states is critical to animal survival. Here the authors show that Capa hormone signaling, homologs to mammalian Neuromedin U, helps control homeostasis via regulation of nutrient uptake and energy storage in Drosophila.
Keywords	Science ; Q
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Coordinated RNA-Seq and peptidomics identify neuropeptides and G-protein coupled receptors (GPCRs) in the large pine weevil Hylobius abietis, a major forestry pest

Pandit, Aniruddha A / Lapo Ragionieri / Richard Marley / Joseph G.C. Yeoh / Daegan J.G. Inward / Shireen-Anne Davies / Reinhard Predel / Julian A.T. Dow

Insect biochemistry and molecular biology. 2018 Oct., v. 101

2018

Abstract: Hylobius abietis (Linnaeus), or large pine weevil (Coleoptera, Curculionidae), is a pest of European coniferous forests. In order to gain understanding of the functional physiology of this species, we have assembled a de novo transcriptome of H. abietis, ...

Abstract	Hylobius abietis (Linnaeus), or large pine weevil (Coleoptera, Curculionidae), is a pest of European coniferous forests. In order to gain understanding of the functional physiology of this species, we have assembled a de novo transcriptome of H. abietis, from sequence data obtained by Next Generation Sequencing. In particular, we have identified genes encoding neuropeptides, peptide hormones and their putative G-protein coupled receptors (GPCRs) to gain insights into neuropeptide-modulated processes. The transcriptome was assembled de novo from pooled paired-end, sequence reads obtained from RNA from whole adults, gut and central nervous system tissue samples. Data analysis was performed on the transcripts obtained from the assembly including, annotation, gene ontology and functional assignment as well as transcriptome completeness assessment and KEGG pathway analysis. Pipelines were created using Bioinformatics tools and techniques for prediction and identification of neuropeptides and neuropeptide receptors. Peptidomic analysis was also carried out using a combination of MALDI-TOF as well as Q-Exactive Orbitrap mass spectrometry to confirm the identified neuropeptide. 41 putative neuropeptide families were identified in H. abietis, including Adipokinetic hormone (AKH), CAPA and DH31. Neuropeptide F, which has not been yet identified in the model beetle T. castaneum, was identified. Additionally, 24 putative neuropeptide and 9 leucine-rich repeat containing G protein coupled receptor-encoding transcripts were determined using both alignment as well as non-alignment methods. This information, submitted to the NCBI sequence read archive repository (SRA accession: SRP133355), can now be used to inform understanding of neuropeptide-modulated physiology and behaviour in H. abietis; and to develop specific neuropeptide-based tools for H. abietis control.
Keywords	G-protein coupled receptors ; Hylobius abietis ; RNA ; adipokinetic hormone ; adults ; bioinformatics ; central nervous system ; coniferous forests ; digestive system ; forestry ; gene ontology ; genes ; high-throughput nucleotide sequencing ; matrix-assisted laser desorption-ionization mass spectrometry ; models ; neuropeptide receptors ; neuropeptides ; pests ; pipelines ; prediction ; transcriptome
Language	English
Dates of publication	2018-10
Size	p. 94-107.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	1483248-3
ISSN	1879-0240 ; 0965-1748
ISSN (online)	1879-0240
ISSN	0965-1748
DOI	10.1016/j.ibmb.2018.08.003
Database	NAL-Catalogue (AGRICOLA)

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Article: The D. melanogaster capa-1 neuropeptide activates renal NF-kB signaling

Terhzaz, Selim / Gayle Overend / Julian A.T. Dow / Shireen-A. Davies / Sujith Sebastian

Peptides. 2014 Mar., v. 53

2014

Abstract: The capa peptide family exists in a very wide range of insects including species of medical, veterinary and agricultural importance. Capa peptides act via a cognate G-protein coupled receptor (capaR) and have a diuretic action on the Malpighian tubules ... ...

Abstract	The capa peptide family exists in a very wide range of insects including species of medical, veterinary and agricultural importance. Capa peptides act via a cognate G-protein coupled receptor (capaR) and have a diuretic action on the Malpighian tubules of Dipteran and Lepidopteran species. Capa signaling is critical for fluid homeostasis and has been associated with desiccation tolerance in the fly, Drosophila melanogaster. The mode of capa signaling is highly complex, affecting calcium, nitric oxide and cyclic GMP pathways. Such complex physiological regulation by cell signaling pathways may occur ultimately for optimal organismal stress tolerance to multiple stressors. Here we show that D. melanogaster capa-1 (Drome-capa-1) acts via the Nuclear Factor kappa B (NF-kB) stress signaling network. Human PCR gene arrays of capaR-transfected Human Embryonic Kidney (HEK) 293 cells showed that Drome-capa-1 increases expression of NF-kB, NF-kB regulated genes including IL8, TNF and PTGS2, and NF-kB pathway-associated transcription factors i.e. EGR1, FOS, cJUN. Furthermore, desiccated HEK293 cells show increased EGR1, EGR3 and PTGS2 – but not IL8, expression. CapaR-transfected NF-kB reporter cells showed that Drome-capa-1 increased NF-kB promoter activity via increased calcium. In Malpighian tubules, both Drome-capa-1 stimulation and desiccation result in increased gene expression of the D. melanogaster NF-kB orthologue, Relish; as well as EGR-like stripe and klumpfuss. Drome-capa-1 also induces Relish translocation in tubule principal cells. Targeted knockdown of Relish in only tubule principal cells reduces desiccation stress tolerance of adult flies. Together, these data suggest that Drome-capa-1 acts in desiccation stress tolerance, by activating NF-kB signaling.
Keywords	calcium ; cyclic GMP ; Drosophila melanogaster ; drought tolerance ; genes ; G-protein coupled receptors ; guanosine monophosphate ; homeostasis ; humans ; imagos ; insects ; interleukin-8 ; kidneys ; Lepidoptera ; Malpighian tubules ; neuropeptides ; nitric oxide ; polymerase chain reaction ; signal transduction ; stress tolerance ; transcription factor NF-kappa B ; tumor necrosis factors
Language	English
Dates of publication	2014-03
Size	p. 218-224.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	769028-9
ISSN	1873-5169 ; 0196-9781
ISSN (online)	1873-5169
ISSN	0196-9781
DOI	10.1016/j.peptides.2013.08.004
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: cGMP signaling pathway that modulates NF-κB activation in innate immune responses

iScience, Vol 24, Iss 12, Pp 103473- (2021)

2021

Abstract: Summary: The nuclear factor-kappa B (NF-κB) pathway is an evolutionarily conserved signaling pathway that plays a central role in immune responses and inflammation. Here, we show that Drosophila NF-κB signaling is activated via a pathway in parallel with ...

Abstract	Summary: The nuclear factor-kappa B (NF-κB) pathway is an evolutionarily conserved signaling pathway that plays a central role in immune responses and inflammation. Here, we show that Drosophila NF-κB signaling is activated via a pathway in parallel with the Toll receptor by receptor-type guanylate cyclase, Gyc76C. Gyc76C produces cyclic guanosine monophosphate (cGMP) and modulates NF-κB signaling through the downstream Tollreceptor components dMyd88, Pelle, Tube, and Dif/Dorsal (NF-κB). The cGMP signaling pathway comprises a membrane-localized cGMP-dependent protein kinase (cGK) called DG2 and protein phosphatase 2A (PP2A) and is crucial for host survival against Gram-positive bacterial infections in Drosophila. A membrane-bound cGK, PRKG2, also modulates NF-κB activation via PP2A in human cells, indicating that modulation of NF-κB activation in innate immunity by the cGMP signaling pathway is evolutionarily conserved.
Keywords	Biological sciences ; Immune response ; Genomics ; Science ; Q
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Metabolomic profiling of permethrin-treated Drosophila melanogaster identifies a role for tryptophan catabolism in insecticide survival

Brinzer, Robert A / Louise Henderson / Alan A. Marchiondo / Debra J. Woods / Shireen A. Davies / Julian A.T. Dow

Insect biochemistry and molecular biology. 2015 Dec., v. 67

2015

Abstract: Insecticides and associated synergists are rapidly losing efficacy in target insect pest populations making the discovery of alternatives a priority. To discover novel targets for permethrin synergists, metabolomics was performed on permethrin-treated ... ...

Abstract	Insecticides and associated synergists are rapidly losing efficacy in target insect pest populations making the discovery of alternatives a priority. To discover novel targets for permethrin synergists, metabolomics was performed on permethrin-treated Drosophila melanogaster. Changes were observed in several metabolic pathways including those for amino acids, glycogen, glycolysis, energy, nitrogen, NAD+, purine, pyrimidine, lipids and carnitine. Markers for acidosis, ammonia stress, oxidative stress and detoxification responses were also observed. Many of these changes had not been previously characterized after permethrin exposure. From the altered pathways, tryptophan catabolism was selected for further investigation. The knockdown of some tryptophan catabolism genes (vermilion, cinnabar and CG6950) in the whole fly and in specific tissues including fat body, midgut and Malpighian tubules using targeted RNAi resulted in altered survival phenotypes against acute topical permethrin exposure. The knockdown of vermilion, cinnabar and CG6950 in the whole fly also altered survival phenotypes against chronic oral permethrin, fenvalerate, DDT, chlorpyriphos and hydramethylnon exposure. Thus tryptophan catabolism has a previously uncharacterized role in defence against insecticides, and shows that metabolomics is a powerful tool for target identification in pesticide research.
Keywords	DDT (pesticide) ; Drosophila melanogaster ; Malpighian tubules ; RNA interference ; acidosis ; ammonia ; biochemical pathways ; carnitine ; chlorpyrifos ; energy ; fat body ; fenvalerate ; genes ; glycogen ; glycolysis ; hydramethylnon ; insect pests ; lipids ; metabolomics ; midgut ; nitrogen ; oxidative stress ; permethrin ; phenotype ; synergists ; tryptophan
Language	English
Dates of publication	2015-12
Size	p. 74-86.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	1483248-3
ISSN	1879-0240 ; 0965-1748
ISSN (online)	1879-0240
ISSN	0965-1748
DOI	10.1016/j.ibmb.2015.09.009
Database	NAL-Catalogue (AGRICOLA)

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Article: A novel role of Drosophila cytochrome P450-4e3 in permethrin insecticide tolerance

Terhzaz, Selim / Pablo Cabrero / Robert A. Brinzer / Kenneth A. Halberg / Julian A.T. Dow / Shireen-A. Davies

Insect biochemistry and molecular biology. 2015 Dec., v. 67

2015

Abstract: The exposure of insects to xenobiotics, such as insecticides, triggers a complex defence response necessary for survival. This response includes the induction of genes that encode key Cytochrome P450 monooxygenase detoxification enzymes. Drosophila ... ...

Abstract	The exposure of insects to xenobiotics, such as insecticides, triggers a complex defence response necessary for survival. This response includes the induction of genes that encode key Cytochrome P450 monooxygenase detoxification enzymes. Drosophila melanogaster Malpighian (renal) tubules are critical organs in the detoxification and elimination of these foreign compounds, so the tubule response induced by dietary exposure to the insecticide permethrin was examined. We found that expression of the gene encoding Cytochrome P450-4e3 (Cyp4e3) is significantly up-regulated by Drosophila fed on permethrin and that manipulation of Cyp4e3 levels, specifically in the principal cells of the Malpighian tubules, impacts significantly on the survival of permethrin-fed flies. Both dietary exposure to permethrin and Cyp4e3 knockdown cause a significant elevation of oxidative stress-associated markers in the tubules, including H2O2 and lipid peroxidation byproduct, HNE (4-hydroxynonenal). Thus, Cyp4e3 may play an important role in regulating H2O2 levels in the endoplasmic reticulum (ER) where it resides, and its absence triggers a JAK/STAT and NF-ÎºB-mediated stress response, similar to that observed in cells under ER stress. This work increases our understanding of the molecular mechanisms of insecticide detoxification and provides further evidence of the oxidative stress responses induced by permethrin metabolism.
Keywords	Drosophila melanogaster ; Malpighian tubules ; cytochrome P-450 ; dietary exposure ; endoplasmic reticulum ; enzymes ; gene expression ; gene expression regulation ; genes ; hydrogen peroxide ; insecticide resistance ; insects ; lipid peroxidation ; metabolism ; oxidative stress ; permethrin ; stress response ; xenobiotics
Language	English
Dates of publication	2015-12
Size	p. 38-46.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	1483248-3
ISSN	1879-0240 ; 0965-1748
ISSN (online)	1879-0240
ISSN	0965-1748
DOI	10.1016/j.ibmb.2015.06.002
Database	NAL-Catalogue (AGRICOLA)

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Article: DINeR: Database for Insect Neuropeptide Research

Yeoh, Joseph G.C / Aniruddha A. Pandit / Dick R. Nässel / Julian A.T. Dow / Meet Zandawala / Shireen-Anne Davies

Insect biochemistry and molecular biology. 2017 July, v. 86

2017

Abstract: Neuropeptides are responsible for regulating a variety of functions, including development, metabolism, water and ion homeostasis, and as neuromodulators in circuits of the central nervous system. Numerous neuropeptides have been identified and ... ...

Abstract	Neuropeptides are responsible for regulating a variety of functions, including development, metabolism, water and ion homeostasis, and as neuromodulators in circuits of the central nervous system. Numerous neuropeptides have been identified and characterized. However, both discovery and functional characterization of neuropeptides across the massive Class Insecta has been sporadic. To leverage advances in post-genomic technologies for this rapidly growing field, insect neuroendocrinology requires a consolidated, comprehensive and standardised resource for managing neuropeptide information.The Database for Insect Neuropeptide Research (DINeR) is a web-based database-application used for search and retrieval of neuropeptide information of various insect species detailing their isoform sequences, physiological functionality and images of their receptor-binding sites, in an intuitive, accessible and user-friendly format. The curated data includes representatives of 50 well described neuropeptide families from over 400 different insect species. Approximately 4700 FASTA formatted, neuropeptide isoform amino acid sequences and over 200 records of physiological functionality have been recorded based on published literature. Also available are images of neuropeptide receptor locations. In addition, the data include comprehensive summaries for each neuropeptide family, including their function, location, known functionality, as well as cladograms, sequence alignments and logos covering most insect orders. Moreover, we have adopted a standardised nomenclature to address inconsistent classification of neuropeptides.As part of the H2020 nEUROSTRESSPEP project, the data will be actively maintained and curated, ensuring a comprehensive and standardised resource for the scientific community. DINeR is publicly available at the project website: http://www.neurostresspep.eu/diner/.
Keywords	amino acid sequences ; central nervous system ; databases ; homeostasis ; Insecta ; insects ; Internet ; metabolism ; neuropeptide receptors ; neuropeptides ; neurotransmitters ; records ; sequence alignment
Language	English
Dates of publication	2017-07
Size	p. 9-19.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	1483248-3
ISSN	1879-0240 ; 0965-1748
ISSN (online)	1879-0240
ISSN	0965-1748
DOI	10.1016/j.ibmb.2017.05.001
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Mapping an atlas of tissue-specific Drosophila melanogaster metabolomes by high resolution mass spectrometry.

Venkateswara R Chintapalli / Mohammed Al Bratty / Dominika Korzekwa / David G Watson / Julian A T Dow

PLoS ONE, Vol 8, Iss 10, p e

2013 Volume 78066

Abstract: Metabolomics can provide exciting insights into organismal function, but most work on simple models has focussed on the whole organism metabolome, so missing the contributions of individual tissues. Comprehensive metabolite profiles for ten tissues from ... ...

Abstract	Metabolomics can provide exciting insights into organismal function, but most work on simple models has focussed on the whole organism metabolome, so missing the contributions of individual tissues. Comprehensive metabolite profiles for ten tissues from adult Drosophila melanogaster were obtained here by two chromatographic methods, a hydrophilic interaction (HILIC) method for polar metabolites and a lipid profiling method also based on HILIC, in combination with an Orbitrap Exactive instrument. Two hundred and forty two polar metabolites were putatively identified in the various tissues, and 251 lipids were observed in positive ion mode and 61 in negative ion mode. Although many metabolites were detected in all tissues, every tissue showed characteristically abundant metabolites which could be rationalised against specific tissue functions. For example, the cuticle contained high levels of glutathione, reflecting a role in oxidative defence; the alimentary canal (like vertebrate gut) had high levels of acylcarnitines for fatty acid metabolism, and the head contained high levels of ether lipids. The male accessory gland uniquely contained decarboxylated S-adenosylmethionine. These data thus both provide valuable insights into tissue function, and a reference baseline, compatible with the FlyAtlas.org transcriptomic resource, for further metabolomic analysis of this important model organism, for example in the modelling of human inborn errors of metabolism, aging or metabolic imbalances such as diabetes.
Keywords	Medicine ; R ; Science ; Q
Subject code	500
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The cell adhesion molecule Fasciclin2 regulates brush border length and organization in Drosophila renal tubules

Kenneth A. Halberg / Stephanie M. Rainey / Iben R. Veland / Helen Neuert / Anthony J. Dornan / Christian Klämbt / Shireen-Anne Davies / Julian A. T. Dow

Nature Communications, Vol 7, Iss 1, Pp 1-

2016 Volume 10

Abstract: In Drosophila, Fasciclin 2 (Fas2) has been mainly studied in the nervous system, yet this adhesion protein is more abundant in the adult renal tubule. Here the authors show that Fas2 is essential for brush border maintenance in renal tubules through ... ...

Abstract	In Drosophila, Fasciclin 2 (Fas2) has been mainly studied in the nervous system, yet this adhesion protein is more abundant in the adult renal tubule. Here the authors show that Fas2 is essential for brush border maintenance in renal tubules through regulation of microvilli length and organization.
Keywords	Science ; Q
Language	English
Publishing date	2016-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: A comprehensive transcriptomic view of renal function in the malaria vector, Anopheles gambiae

Overend, Gayle / Pablo Cabrero / Kenneth A. Halberg / Lisa C. Ranford-Cartwright / Debra J. Woods / Shireen A. Davies / Julian A.T. Dow

Insect biochemistry and molecular biology. 2015 Dec., v. 67

2015

Abstract: Renal function is essential to maintain homeostasis. This is particularly significant for insects that undergo complete metamorphosis; larval mosquitoes must survive a freshwater habitat whereas adults are terrestrial, and mature females must maintain ... ...

Abstract	Renal function is essential to maintain homeostasis. This is particularly significant for insects that undergo complete metamorphosis; larval mosquitoes must survive a freshwater habitat whereas adults are terrestrial, and mature females must maintain ion and fluid homeostasis after blood feeding. To investigate the physiological adaptations required for successful development to adulthood, we studied the Malpighian tubule transcriptome of Anopheles gambiae using Affymetrix arrays. We assessed transcription under several conditions; as third instar larvae, as adult males fed on sugar, as adult females fed on sugar, and adult females after a blood meal. In addition to providing the most detailed transcriptomic data to date on the Anopheles Malpighian tubules, the data provide unique information on the renal adaptations required for the switch from freshwater to terrestrial habitats, on gender differences, and on the contrast between nectar-feeding and haematophagy. We found clear differences associated with ontogenetic change in lifestyle, gender and diet, particularly in the neuropeptide receptors that control fluid secretion, and the water and ion transporters that impact volume and composition. These data were also combined with transcriptomics from the Drosophila melanogaster tubule, allowing meta-analysis of the genes which underpin tubule function across Diptera. To further investigate renal conservation across species we selected four D. melanogaster genes with orthologues highly enriched in the Anopheles tubules, and generated RNAi knockdown flies. Three of these genes proved essential, showing conservation of critical functions across 150 million years of phylogenetic separation. This extensive data-set is available as an online resource, MozTubules.org, and could potentially be mined for novel insecticide targets that can impact this critical organ in this pest species.
Keywords	Anopheles gambiae ; Drosophila melanogaster ; Malpighian tubules ; RNA interference ; adulthood ; adults ; data collection ; diet ; females ; freshwater ; gender differences ; genes ; habitats ; hematophagy ; homeostasis ; insect vectors ; insecticides ; instars ; larvae ; lifestyle ; males ; meta-analysis ; metamorphosis ; nectar feeding ; neuropeptide receptors ; ontogeny ; pests ; phylogeny ; renal function ; secretion ; sugars ; transcription (genetics) ; transcriptome ; transcriptomics ; transporters
Language	English
Dates of publication	2015-12
Size	p. 47-58.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	1483248-3
ISSN	1879-0240 ; 0965-1748
ISSN (online)	1879-0240
ISSN	0965-1748
DOI	10.1016/j.ibmb.2015.05.007
Database	NAL-Catalogue (AGRICOLA)

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