Sugar feeding protects against arboviral infection by enhancing gut immunity in the mosquito vector Aedes aegypti.

As mosquito females require a blood meal to reproduce, they can act as vectors of numerous pathogens, such as arboviruses (e.g. Zika, dengue and chikungunya viruses), which constitute a substantial worldwide public health burden.

A nutrient-responsive hormonal circuit mediates an inter-tissue program regulating metabolic homeostasis in adult Drosophila.

Animals maintain metabolic homeostasis by modulating the activity of specialized organs that adjust internal metabolism to external conditions. However, the hormonal signals coordinating these functions are incompletely characterized. Here we show that six neurosecretory cells in the Drosophila central nervous system respond to circulating nutrient levels by releasing Capa hormones, homologs of mammalian neuromedin U, which activate the Capa receptor (CapaR) in peripheral tissues to control energy homeostasis.

Specialized stellate cells offer a privileged route for rapid water flux in renal tubule.

Insects are highly successful, in part through an excellent ability to osmoregulate. The renal (Malpighian) tubules can secrete fluid faster on a per-cell basis than any other epithelium, but the route for these remarkable water fluxes has not been established. In , we show that 4 genes of the major intrinsic protein family are expressed at a very high level in the fly renal tissue: the aquaporins (AQPs) and and the aquaglyceroporins and As predicted from their structure, and by their transport function by expressing these proteins in oocytes, Drip, Prip, and Eglp2 show significant and specific water permeability, whereas Eglp2 and Eglp4 show very high permeability to glycerol and urea.

Targeted renal knockdown of Na/H exchanger regulatory factor produces uric acid nephrolithiasis in .

Nephrolithiasis is one of the most common kidney diseases, with poorly understood pathophysiology, but experimental study has been hindered by lack of experimentally tractable models. is a useful model organism for renal diseases because of genetic and functional similarities of Malpighian (renal) tubules with the human kidney. Here, we demonstrated function of the sex-determining region Y protein-interacting protein-1 () gene, an ortholog of human Na/H exchanger regulatory factor (), in Malpighian tubules and its impact on nephrolithiasis.

Novel roles for in growth, maintenance and proliferation of cell populations in the renal tubule.

The GATA family of transcription factors is implicated in numerous developmental and physiological processes in metazoans. In , five different GATA factor genes (, , , and ) have been reported as essential in the development and identity of multiple tissues, including the midgut, heart and brain. Here, we present a novel role for in the function and homeostasis of the renal (Malpighian) tubule.

Renal neuroendocrine control of desiccation and cold tolerance by Drosophila suzukii.

Background: Neuropeptides are central to the regulation of physiological and behavioural processes in insects, directly impacting cold and desiccation survival. However, little is known about the control mechanisms governing these responses in Drosophila suzukii. The close phylogenetic relationship of D.

The corticotropin-releasing factor-like diuretic hormone 44 (DH44) and kinin neuropeptides modulate desiccation and starvation tolerance in Drosophila melanogaster.

Malpighian tubules are critical organs for epithelial fluid transport and stress tolerance in insects, and are under neuroendocrine control by multiple neuropeptides secreted by identified neurons. Here, we demonstrate roles for CRF-like diuretic hormone 44 (DH44) and Drosophila melanogaster kinin (Drome-kinin, DK) in desiccation and starvation tolerance. Gene expression and labelled DH44 ligand binding data, as well as highly selective knockdowns and/or neuronal ablations of DH44 in neurons of the pars intercerebralis and DH44 receptor (DH44-R2) in Malpighian tubule principal cells, indicate that suppression of DH44 signalling improves desiccation tolerance of the intact fly.

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

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.

Tracing the evolutionary origins of insect renal function.

Knowledge on neuropeptide receptor systems is integral to understanding animal physiology. Yet, obtaining general insight into neuropeptide signalling in a clade as biodiverse as the insects is problematic. Here we apply fluorescent analogues of three key insect neuropeptides to map renal tissue architecture across systematically chosen representatives of the major insect Orders, to provide an unprecedented overview of insect renal function and control.

Insect capa neuropeptides impact desiccation and cold tolerance.

The success of insects is linked to their impressive tolerance to environmental stress, but little is known about how such responses are mediated by the neuroendocrine system. Here we show that the capability (capa) neuropeptide gene is a desiccation- and cold stress-responsive gene in diverse dipteran species. Using targeted in vivo gene silencing, physiological manipulations, stress-tolerance assays, and rationally designed neuropeptide analogs, we demonstrate that the Drosophila melanogaster capa neuropeptide gene and its encoded peptides alter desiccation and cold tolerance.

Chloride channels in stellate cells are essential for uniquely high secretion rates in neuropeptide-stimulated Drosophila diuresis.

Epithelia frequently segregate transport processes to specific cell types, presumably for improved efficiency and control. The molecular players underlying this functional specialization are of particular interest. In Drosophila, the renal (Malpighian) tubule displays the highest per-cell transport rates known and has two main secretory cell types, principal and stellate.

Cell signalling mechanisms for insect stress tolerance.

Insects successfully occupy most environmental niches and this success depends on surviving a broad range of environmental stressors including temperature, desiccation, xenobiotic, osmotic and infection stress. Epithelial tissues play key roles as barriers between the external and internal environments and therefore maintain homeostasis and organismal tolerance to multiple stressors. As such, the crucial role of epithelia in organismal stress tolerance cannot be underestimated.

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

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.

Signaling by Drosophila capa neuropeptides.

The capa peptide family, originally identified in the tobacco hawk moth, Manduca sexta, is now known to be present in many insect families, with increasing publications on capa neuropeptides each year. The physiological actions of capa peptides vary depending on the insect species but capa peptides have key myomodulatory and osmoregulatory functions, depending on insect lifestyle, and life stage. Capa peptide signaling is thus critical for fluid homeostasis and survival, making study of this neuropeptide family attractive for novel routes for insect control.

Functional correlates of positional and gender-specific renal asymmetry in Drosophila.

Background: In humans and other animals, the internal organs are positioned asymmetrically in the body cavity, and disruption of this body plan can be fatal in humans. The mechanisms by which internal asymmetry are established are presently the subject of intense study; however, the functional significance of internal asymmetry (outside the brain) is largely unexplored. Is internal asymmetry functionally significant, or merely an expedient way of packing organs into a cavity?

Methodology/principal Findings: Like humans, Drosophila shows internal asymmetry, with the gut thrown into stereotyped folds.

Immune and stress response 'cross-talk' in the Drosophila Malpighian tubule.

The success of insects is in large part due to their ability to survive environmental stress, including heat, cold, and dehydration. Insects are also exposed to infection, osmotic or oxidative stress, and to xenobiotics or toxins. The molecular mechanisms of stress sensing and response have been widely investigated in mammalian cell lines, and the area of stress research is now so vast to be beyond the scope of a single review article.

Mechanism and function of Drosophila capa GPCR: a desiccation stress-responsive receptor with functional homology to human neuromedinU receptor.

The capa peptide receptor, capaR (CG14575), is a G-protein coupled receptor (GPCR) for the D. melanogaster capa neuropeptides, Drm-capa-1 and -2 (capa-1 and -2). To date, the capa peptide family constitutes the only known nitridergic peptides in insects, so the mechanisms and physiological function of ligand-receptor signalling of this peptide family are of interest.

Cell-specific inositol 1,4,5 trisphosphate 3-kinase mediates epithelial cell apoptosis in response to oxidative stress in Drosophila.

Organismal stress responses to oxidative stress are relevant to ageing and disease and involve key cell-/tissue-specific signal transduction mechanisms. Using Drosophila, an established in vivo model for stress studies, we show that cell-specific inositol phosphate signalling specifically via inositol 1,4,5 trisphosphate 3-kinase (InsP(3) 3-K, IP(3)K), negatively regulates organismal responses to oxidative stress. We demonstrate that the Drosophila Malpighian tubule (equivalent to vertebrate kidney and liver) is a key epithelial sensor for organismal oxidative stress responses: precise targeting of either gain-of-function constructs of Drosophila IP(3)Ks (IP(3)K-1 and IP(3)K-2), or loss-of-function (RNAi) constructs to only one cell type in tubule reversibly modulates survival of stress-challenged adult flies.

Mislocalization of mitochondria and compromised renal function and oxidative stress resistance in Drosophila SesB mutants.

Mitochondria accumulate at sites of intense metabolic activity within cells, but the adaptive value of this placement is not clear. In Drosophila, sesB encodes the ubiquitous isoform of adenine nucleotide translocase (ANT, the mitochondrial inner membrane ATP/ADP exchanger); null alleles are lethal, whereas hypomorphic alleles display sensitivity to a range of stressors. In the adult renal tubule, which is densely packed with mitochondria and hence enriched for sesB, both hypomorphic alleles and RNA interference knockdowns cause the mitochondria to lose their highly polarized distribution in the tissue and to become rounded.

Organellar calcium signalling mechanisms in Drosophila epithelial function.

Calcium signalling and calcium homeostasis are essential for life. Studies of calcium signalling thus constitute a major proportion of research in the life sciences, although the majority of these studies are based in cell lines or isolated cells. Epithelial cells and tissues are essential in the regulation of critical physiological processes, including fluid transport; and so the modulation of such processes in vivo by cell-specific calcium signalling is thus of interest.

A Drosophila systems approach to xenobiotic metabolism.

Insecticide resistance is a major problem for both medicine and agriculture and is frequently associated with overexpression of metabolic enzymes that catalyze the breakdown of pesticides, leading to broad-spectrum resistance. However, the insect tissues within which these metabolic enzymes normally reside remain unclear. Microarray analysis of nine adult tissues from Drosophila melanogaster reveals that cytochrome P-450s and glutathione-S-transferases show highly tissue-specific expression patterns; most were confined to one or more epithelial tissues, and half showed dominant expression in a single tissue.

The neuropeptide SIFamide modulates sexual behavior in Drosophila.

The expression of Drosophila neuropeptide AYRKPPFNGSIFamide (SIFamide) was shown by both immunohistology and in situ hybridization to be restricted to only four neurons of the pars intercerebralis. The role of SIFamide in adult courtship behavior in both sexes was studied using two different approaches to perturb the function of SIFamide; targeted cell ablation and RNA interference (RNAi). Elimination of SIFamide by either of these methods results in promiscuous flies; males perform vigorous and indiscriminant courtship directed at either sex, while females appear sexually hyper-receptive.

Differential gel electrophoresis and transgenic mitochondrial calcium reporters demonstrate spatiotemporal filtering in calcium control of mitochondria.

Mitochondria must adjust both their intracellular location and their metabolism in order to balance their output to the needs of the cell. Here we show by the proteomic technique of time series difference gel electrophoresis that a major result of neuroendocrine stimulation of the Drosophila renal tubule is an extensive remodeling of the mitochondrial matrix. By generating Drosophila that were transgenic for both luminescent and fluorescent mitochondrial calcium reporters, it was shown that mitochondrial calcium tracked the slow (minutes) but not the rapid (<1 s) changes in cytoplasmic calcium and that this resulted in both increased mitochondrial membrane polarization and elevated cellular ATP levels.

Novel subcellular locations and functions for secretory pathway Ca2+/Mn2+-ATPases.

Secretory pathway Ca2+/Mn2+-ATPases (SPCAs) are important for maintenance of cellular Ca2+ and Mn2+ homeostasis, and, to date, all SPCAs have been found to localize to the Golgi apparatus. The single Drosophila SPCA gene (SPoCk) was identified by an in silico screen for novel Ca2+-ATPases. It encoded three SPoCk isoforms with novel, distinct subcellular specificities in the endoplasmic reticulum (ER) and peroxisomes in addition to the Golgi.