Explore the vast range of titles available.

Insects have evolved a variety of neurohormones that enable them to maintain nutrient and osmotic homeostasis. Here, we characterized the ion transport peptide (ITP) signaling system in Drosophila . The Drosophila ITP gene can generate three different peptide isoforms: ITP amidated (ITPa) and two ITP-like (ITPL1 and ITPL2) isoforms. We comprehensively characterized the expression of all three ITP isoforms in the nervous system and peripheral tissues. Our analyses reveal widespread expression of ITP isoforms. Moreover, we show that ITPa-producing neurons are activated and release ITPa during dehydration. Furthermore, recombinant Drosophila ITPa inhibits diuretic peptide-induced renal tubule secretion ex vivo, thus confirming its role as an anti-diuretic hormone. Using a phylogenetic-driven approach, an ex vivo secretion assay and a heterologous mammalian cell-based assay, we identified and functionally characterized Gyc76C, a membrane guanylate cyclase, as a bona fide Drosophila ITPa receptor. Extensive anatomical mapping of Gyc76C reveals that it is highly expressed in larval and adult tissues associated with osmoregulation (renal tubules and rectum) and metabolic homeostasis (fat body). Consistent with this expression, knockdown of Gyc76C in renal tubules impacts tolerance to osmotic and ionic stresses, whereas knockdown specifically in the fat body impacts feeding, nutrient homeostasis, and associated behaviors. We also complement receptor knockdown experiments with ITP knockdown and ITPa overexpression in ITPa-producing neurons. Lastly, we utilized connectomics and single-cell transcriptomics to identify pathways via which ITP neurons integrate hygrosensory inputs and interact with other homeostatic hormonal pathways. Taken together, our systematic characterization of ITP signaling establishes a tractable system to decipher how a small set of neurons integrates diverse inputs to orchestrate systemic homeostasis in Drosophila .

Insects have evolved a variety of neurohormones that enable them to maintain nutrient and osmotic homeostasis. Here, we characterized the ion transport peptide (ITP) signaling system in Drosophila . The Drosophila ITP gene can generate three different peptide isoforms: ITP amidated (ITPa) and two ITP-like (ITPL1 and ITPL2) isoforms. We comprehensively characterized the expression of all three ITP isoforms in the nervous system and peripheral tissues. Our analyses reveal widespread expression of ITP isoforms. Moreover, we show that ITPa-producing neurons are activated and release ITPa during dehydration. Furthermore, recombinant Drosophila ITPa inhibits diuretic peptide-induced renal tubule secretion ex vivo, thus confirming its role as an anti-diuretic hormone. Using a phylogenetic-driven approach, an ex vivo secretion assay and a heterologous mammalian cell-based assay, we identified and functionally characterized Gyc76C, a membrane guanylate cyclase, as a bona fide Drosophila ITPa receptor. Extensive anatomical mapping of Gyc76C reveals that it is highly expressed in larval and adult tissues associated with osmoregulation (renal tubules and rectum) and metabolic homeostasis (fat body). Consistent with this expression, knockdown of Gyc76C in renal tubules impacts tolerance to osmotic and ionic stresses, whereas knockdown specifically in the fat body impacts feeding, nutrient homeostasis, and associated behaviors. We also complement receptor knockdown experiments with ITP knockdown and ITPa overexpression in ITPa-producing neurons. Lastly, we utilized connectomics and single-cell transcriptomics to identify pathways via which ITP neurons integrate hygrosensory inputs and interact with other homeostatic hormonal pathways. Taken together, our systematic characterization of ITP signaling establishes a tractable system to decipher how a small set of neurons integrates diverse inputs to orchestrate systemic homeostasis in Drosophila .

Due to dynamic environmental conditions including temperature, water and food availability, insects like the model organism Drosophila melanogaster, must modulate their internal physiology to withstand these challenges. Regulation of the excretory system by peptidergic hormones is one mechanism by which insects maintain their internal homeostasis. Tachykinins are a family of neuropeptides that have been shown to stimulate fluid secretion from the Malpighian \"renal\" tubules (MTs) in some insect species, but it is unclear if that is the case in the fruit fly, D. melanogaster. A central objective of the current study was to examine the physiological role of tachykinin signaling in the MTs of adult D. melanogaster. Using the genetic toolbox available in this model organism along with in vitro and whole animal bioassays, our results indicate that Drosophila tachykinins (DTKs) function as diuretic hormones by binding to the DTK receptor (DTKR) expressed in stellate cells of the MTs. Specifically, DTK activates cation and anion transport across the stimulated MTs, which negatively impacts their survival in response to desiccation due to their inability to conserve water. Thus, besides their previously described roles in neuromodulation of pathways controlling locomotion and food search, olfactory processing, aggression, lipid metabolism and metabolic stress, processing of noxious stimuli and hormone release, DTKs also appear to function as bona fide endocrine factors regulating the excretory system and appear essential for the maintenance of hydromineral balance.Competing Interest StatementThe authors have declared no competing interest.

Insects have evolved a variety of neurohormones that enable them to maintain their nutrient and osmotic homeostasis. While the identities and functions of various insect metabolic and diuretic hormones have been well-established, the characterization of an anti-diuretic signaling system that is conserved across most insects is still lacking. To address this, here we characterized the ion transport peptide (ITP) signaling system in Drosophila. The Drosophila ITP gene encodes five transcript variants which generate three different peptide isoforms: ITP amidated (ITPa) and two ITP-like (ITPL1 and ITPL2) isoforms. Using a combination of anatomical mapping and single-cell transcriptome analyses, we comprehensively characterized the expression of all three ITP isoforms in the nervous system and peripheral tissues. Our analyses reveal wide-spread expression of ITP isoforms. Moreover, we show that ITPa-producing neurons are activated and release ITPa during dehydration. Further, recombinant Drosophila ITPa inhibits diuretic peptide-induced renal tubule secretion ex vivo, thus confirming its role as an anti-diuretic hormone. Using a phylogenetic-driven approach, an ex vivo secretion assay and a heterologous mammalian cell-based assay, we identified and functionally characterized Gyc76C, a membrane guanylate cyclase, as a bona fide Drosophila ITPa receptor. Thus, recombinant ITPa application leads to increased cGMP production in HEK293T cells expressing Drosophila Gyc76C. Moreover, knockdown of Gyc76C in renal tubules abolishes the inhibitory effect of ITPa on diuretic hormone stimulated secretion. Extensive anatomical mapping of Gyc76C reveals that it is highly expressed in larval and adult tissues associated with osmoregulation (renal tubules and rectum) and metabolic homeostasis (fat body). Consistent with this expression, knockdown of Gyc76C in renal tubules impacts tolerance to osmotic and ionic stresses, whereas knockdown specifically in the fat body impacts feeding, nutrient homeostasis and associated behaviors. We also complement receptor knockdown experiments with ITP knockdown and ITPa overexpression in ITPa-producing neurons. Interestingly, the ITPa-Gyc76C pathway examined here is reminiscent of the atrial natriuretic peptide signaling in mammals. Lastly, we utilized connectomics and single-cell transcriptomics to identify synaptic and paracrine pathways upstream and downstream of ITPa-expressing neurons. Our analysis identifies pathways via which ITP neurons integrate hygrosensory inputs and interact with other homeostatic hormonal pathways. Taken together, our systematic characterization of ITP signaling establishes a tractable system to decipher how a small set of neurons integrates diverse inputs to orchestrate systemic homeostasis in Drosophila.