Biology subjects

Koyama, T.

Publications and source records attributed to Koyama, T..

At least 19 recordsLinked to original sources

bioRxiv2025

Quantum Algorithm for Metabolic Network Analysis

Biological systems, such as cellular metabolism, involve thousands of reactions that together determine how cells grow, respond to their environment, and produce energy. Modeling and analyzing these systems require solving very large mathematical problems that can quickly become computationally prohibitive. To address this challenge, we present a quantum algorithm to analyze metabolic networks, focusing on flux balance analysis as a representative case. We use a quantum interior point method consisting of a quantum subroutine for matrix inversion. Specifically, we reformulate the metabolic optimization problem for efficient execution on a quantum computer using quantum singular value transformation, enabling a rapid solution of complex systems that arise in flux balance analysis. This quantum approach offers a potential computational advantage over classical interior point methods for large and well-conditioned networks. We demonstrate the practical applicability of our method with numerical simulations on the glycolysis and tricarboxylic acid (TCA) cycle network and show that the quantum solution converges to the correct biological objective. This work represents the first application of quantum algorithms to metabolic pathway analysis, establishing a new direction for quantum computational biology and paving the way for quantum approaches to large-scale biological optimization.

systems biology↗

bioRxiv2025

Ion transport peptide regulates body water balance via a receptor guanylyl cyclase in the Drosophila hindgut

Maintaining internal water balance, including ionic and osmotic balance, is critical for animal development and survival. In insects, internal water balance is regulated through the Malpighian tubules and the hindgut, which transport water and ions across their epithelia under the regulation of multiple peptide hormones. One of these, ion transport peptide (ITP), a member of the highly conserved crustacean hyperglycemic hormone superfamily among ecdysozoans, is an anti-diuretic hormone in insects, but its mechanism of action remains largely unclear. Here, we show that the short amidated isoform of ITP (saITP), secreted from brain neurosecretory cells, regulates water absorption via the receptor guanylyl cyclase (rGC) Gyc76C in the hindgut of the fruit fly Drosophila melanogaster. Both ITP and Gyc76C are evolutionarily conserved and are essential for larval survival in D. melanogaster, as mutation or knockdown of either gene results in early larval lethality. In Drosophila S2 cells, synthetic saITP increases intracellular cyclic GMP (cGMP) in a Gyc76C-dependent manner, an effect abolished by deletion of its putative ligand-binding domain. Using the fluorescent cGMP biosensor RedcGull in ex vivo-cultured hindguts, we found that saITP increases epithelial cGMP levels, and this response requires Gyc76C. Consistently, saITP promotes hindgut water reabsorption via Gyc76C. Thus, saITP acts via Gyc76C in a brain-hindgut neuroendocrine axis that regulates internal water balance during development. Our study provides new insight into the neuroendocrine control of osmoregulation in ecdysozoans and supports a broader role for rGCs in peptide-hormone signaling.

physiology↗

bioRxiv2025

TCP3-mediated regulation of cell expansion in Arabidopsis thaliana

(1) Cell expansion is crucial for organ morphogenesis in multicellular organisms. Apoplast acidification triggers plant cell expansion. Plant hormones and transcription factors such as TEOSINTE BRANCHED, CYCLOIDEA, and PROLIFERATING CELL NUCLEAR ANTIGEN BINDING FACTORs (TCPs) control cell expansion. However, details regarding the regulatory mechanism of cell expansion for organ morphogenesis remain unclear. (2) In this study, we used molecular, biochemical, cellular, genetic, atomic force microscopy, and tensile testing analyses and showed that miR319-targeted TCPs integrated cell expansion with organ morphogenesis in Arabidopsis thaliana. (3) We found that TCPs directly induce the expression of genes encoding cell wall loosening proteins and SMALL AUXIN UP RNAs (SAURs), activators of plasma membrane-localized H+-ATPases. TCP-mediated activation of plasma membrane- localized H+-ATPases stimulates apoplast acidification, reduce cell stiffness, promote cell expansion, and thus exaggerate elongation of the hypocotyl. Ectopic expression of a SAUR gene in sextuple tcp mutant plants substantially recovered the hypocotyl morphology of the tcp mutant, providing genetic evidence of TCP-mediated SAUR regulation. (4) Collectively, our data show that TCPs regulate apoplast acidification for cell expansion.

plant biology↗

bioRxiv2024

Glia-mediated gut-brain cytokine signaling couples sleep to intestinal inflammation

Sickness-induced sleep is a behavior conserved across species that promotes recovery from illness, yet the underlying mechanisms are poorly understood. Here, we show that interleukin-6-like cytokine signaling from the Drosophila gut to brain glial cells regulates sleep. Under healthy conditions, this pathway promotes wakefulness. However, elevated gut cytokine signaling in response to oxidative stress - triggered by immune and inflammatory responses in the intestine - induces sleep. The cytokines Unpaired 2 and -3 are upregulated by oxidative stress in enteroendocrine cells and activate JAK-STAT signaling in glial cells, including those of the blood-brain barrier (BBB). This activity maintains elevated sleep during oxidative-stress-induced intestinal disturbances, suggesting that the JAK-STAT pathway in glia inhibits wake-promoting signaling to facilitate sleep-dependent restoration under these conditions. We find that the enteric peptide Allatostatin A (AstA) enhances wakefulness, and during intestinal oxidative stress, gut-derived Unpaired 2/3 inhibits AstA receptor expression in BBB glia, thereby sustaining an elevated sleep state during gut inflammation or illness. Taken together, our work identifies a gut-to-glial communication pathway that couples sleep with intestinal homeostasis and disease, enhancing sleep during intestinal sickness, and contributes to our understanding of how sleep disturbances arise from gastrointestinal disturbances.

animal behavior and cognition↗

bioRxiv2024

HR3/RORα-mediated cholesterol sensing regulates TOR signaling

Cells and organisms adjust their growth based on the availability of cholesterol, which is essential for cellular functions. However, the mechanisms by which cells sense cholesterol levels and translate these into growth signals are not fully understood. We report that cholesterol rapidly activates the master growth-regulatory TOR pathway in Drosophila tissues. We identify the nuclear receptor HR3, an ortholog of mammalian ROR, as an essential factor in cholesterol-induced TOR activation. We demonstrate that HR3 binds cholesterol and promotes TOR pathway activation through a non-genomic mechanism acting upstream of the Rag GTPases. Similarly, we find that ROR is necessary for cholesterol-mediated TOR activation in human cells, suggesting that HR3/ROR represents a conserved mechanism for cholesterol sensing that couples cholesterol availability to TOR-pathway activity. These findings advance our understanding of how cholesterol influences cell growth, with implications for cholesterol-related diseases and cancer. HighlightsO_LICholesterol leads to dynamic TOR pathway activation, driving systemic growth C_LIO_LIHR3 in Drosophila binds cholesterol and couples its availability to TOR activation C_LIO_LIHR3 acts upstream of Rag GTPases to activate TOR in response to lysosomal cholesterol C_LIO_LIMammalian HR3 ortholog ROR is required for cholesterol-induced TOR activation C_LI

cell biology↗

bioRxiv2024

Something old, something new: the origins of an unusual renal cell underpinning a beetle water-conserving mechanism

Tenebrionid beetles have been highly successful in colonising environments where water is scarce, underpinned by their unique osmoregulatory adaptations. These include a cryptonephridial arrangement of their organs, in which part of their renal/Malpighian tubules are bound to the surface of the rectum. This allows them to generate a steep osmotic gradient to draw water from within the rectum and return it to the body. Within the cryptonephridial tubules a seemingly novel cell type, the leptophragmata, is considered to play a key role in transporting potassium chloride to generate this osmotic gradient. Nothing was known about the developmental mechanisms or evolution of these unusual renal cells. Here we investigate the mechanisms underpinning development of the leptophragmata in the red flour beetle, Tribolium castaneum. We find that leptophragmata express and require a teashirt/tiptop transcription factor gene, as do the secondary renal cells of Drosophila melanogaster which lack a cryptonephridial arrangement. We also find an additional transcription factor, Dachshund, is required to establish leptophragmata identity and to distinguish them from the secondary cells in Triboliums non-cryptonephridial region of renal tubule. Dachshund is also expressed in a sub-population of secondary cells in Drosophila. So leptophragmata, which are unique to the beetle lineage, appear to have originated from a specific renal cell type present ancestrally, and specified by a conserved repertoire of transcription factors. SignificanceBeetles are a highly successful insect group and represent a quarter of all known animal species. Their digestive/renal systems have undergone major evolutionary change compared to other insects, likely contributing to their success. A dramatic example is the cryptonephridial complex, an evolutionary innovation of the gut and renal system which integrate as a powerful water-conservation system; an adaptation for survival in arid conditions. An unusual renal cell type--the leptophragmata--underpin the functions of the complex, but their developmental and evolutionary origins are unknown. Here we reveal the developmental mechanism that establish leptophragmata identity and, by studying a species lacking a cryptonephridial complex, shed light on their evolutionary origin. More broadly, the work illuminates the evolution of novel cell types.

developmental biology↗

bioRxiv2024

ChemGLaM: Chemical-Genomics Language Models for Compound-Protein Interaction Prediction

Deep learning-based compound-protein interaction (CPI) prediction models are promising in the field of molecular biology, particularly for facilitating the drug discovery process. In practical applications, CPI models should achieve a high generalization performance, quantify prediction confidence, and ensure explainability. Here, we propose ChemGLaM, a chemical genomics language model for reliable and explainable CPI predictions, by addressing these three crucial aspects. ChemGLaM integrates independently pre-trained chemical and protein language models through an interaction block with a cross-attention mechanism, achieving state-of-the-art performance in predicting novel CPIs. Incorporating uncertainty estimation and attention visualization enables ChemGLaM to enhance the success rate of virtual screening and to provide molecular insights into CPIs. Furthermore, we demonstrate its practical applicability by constructing a public database for large-scale CPI predictions and enabling drug/target exploration for candidate treatment of amyotrophic lateral sclerosis (ALS). ChemGLaM represents a significant step toward overcoming the challenges of AI-driven drug discovery and addressing unmet medical needs.

bioinformatics↗

bioRxiv2023

A neuronal relay mediates muscle-adipose communication that drives systemic metabolic adaptation to high-sugar diets

Obesity leads to impaired insulin signaling and tissue sensitivity, which drive the onset of type 2 diabetes. Insulin resistance leads to a reduction in cellular glucose uptake, resulting in elevated blood glucose levels, which consequently cause {beta}-cell dysfunction and development of diabetes. Although improving insulin signaling is a key target for restoring whole-body glucose homeostasis and reversing diabetes, the multi-organ mechanisms that regulate insulin signaling and tissue sensitivity are poorly defined. We screened the secretome and receptome in Drosophila to identify the underlying interorgan hormonal crosstalk affecting diet-induced insulin resistance and obesity. We identified complex interplay between muscle, neuronal, and fat tissues, mediated by the conserved BMP and LGR signaling pathways, which augments insulin signaling and improves dietary sugar tolerance. We found that muscle-derived BMP signaling is induced by sugar and governs neuronal Bursicon signaling. Acting through its LGR-family receptor, Bursicon both enhances insulin secretion and improves insulin sensitivity in adipose tissue, thereby preventing sugar-induced hyperglycemia. Inhibition of Bursicon-LGR signaling in adipose tissue exacerbates sugar-induced insulin resistance, and we discovered that this condition could be alleviated by suppressing NF-{kappa}B signaling. Our findings identify a muscle-neuronal-fat tissue axis that drives metabolic adaptation to high-sugar conditions by modulating insulin secretion and adipocyte insulin sensitivity, highlighting mechanisms that may be exploited for the development of strategies for the treatment and reversal of insulin resistance.

physiology↗

bioRxiv2023

Eosinophils exert direct and indirect anti-tumorigenic effects in the development of esophageal squamous cell carcinoma

Background/AimsEosinophils are present in several solid tumors and have context-dependent function. Our aim is to define the contribution of eosinophils in esophageal squamous cell carcinoma (ESCC), since their role in ESCC is unknown. MethodsEosinophils were enumerated in tissues from two ESCC cohorts. Mice were treated with 4-nitroquinolone-1-oxide (4-NQO) for 8 weeks to induce pre-cancer or 16 weeks to induce carcinoma. Eosinophil number was modified by monoclonal antibody to IL-5 (IL5mAb), recombinant IL-5 (rIL-5), or genetically with eosinophil-deficient ({Delta}dblGATA) mice or mice deficient in eosinophil chemoattractant eotaxin-1 (Ccl11-/-). Esophageal tissue and eosinophil specific RNA-sequencing was performed to understand eosinophil function. 3-D co-culturing of eosinophils with pre-cancer or cancer cells was done to ascertain direct effects of eosinophils. ResultsActivated eosinophils are present in higher numbers in early stage versus late stage ESCC. Mice treated with 4-NQO exhibit more esophageal eosinophils in pre-cancer versus cancer. Correspondingly, epithelial cell Ccl11 expression is higher in mice with pre-cancer. Eosinophil depletion using three mouse models (Ccl11-/- mice, {Delta}dblGATA mice, IL5mAb treatment) all display exacerbated 4-NQO tumorigenesis. Conversely, treatment with rIL-5 increases esophageal eosinophilia and protects against pre-cancer and carcinoma. Tissue and eosinophil RNA-sequencing revealed eosinophils drive oxidative stress in pre-cancer. In vitro co-culturing of eosinophils with pre-cancer or cancer cells resulted in increased apoptosis in the presence of a degranulating agent, which is reversed with N-acetylcysteine, a reactive oxygen species (ROS) scavenger. {Delta}dblGATA mice exhibited increased CD4 T cell infiltration, IL-17, and enrichment of IL-17 pro-tumorigenic pathways. ConclusionEosinophils likely protect against ESCC through ROS release during degranulation and suppression of IL-17.

cancer biology↗

bioRxiv2022

NHA1 is a cation/proton antiporter essential for the water-conserving functions of the rectal complex in Tribolium castaneum

More than half of all extant metazoan species on earth are insects. The evolutionary success of insects is intrinsically linked with their ability to osmoregulate, suggesting that they have evolved unique physiological mechanisms to maintain water balance. In beetles (Coleoptera)--the largest group of insects--a specialized rectal ( cryptonephridial) complex has evolved that recovers water from the rectum destined for excretion and recycles it back to the body. However, the molecular mechanisms underpinning the remarkable waterconserving functions of this system are unknown. Here, we introduce a transcriptomic resource, BeetleAtlas.org, for red flour beetle Tribolium castaneum, and demonstrate its utility by identifying a cation/H+ antiporter (NHA1) that is enriched and functionally significant in the Tribolium rectal complex. NHA1 localizes exclusively to a specialized cell type, the leptophragmata, in the distal region of the Malpighian tubules associated with the rectal complex. Computational modelling and electrophysiological characterization in Xenopus oocytes show that NHA1 acts as an electroneutral K+/H+ antiporter. Furthermore, genetic silencing of Nha1 dramatically increases excretory water loss and reduces organismal survival during desiccation stress, implying that NHA1 activity is essential for maintaining systemic water balance. Finally, we show that Tiptop, a conserved transcription factor, regulates NHA1 expression in leptophragmata and controls leptophragmata maturation, illuminating the developmental mechanism that establishes the novel functions of this cell. Together, our work provides the first insights into the molecular architecture underpinning the function of one most powerful water-conserving mechanisms in nature, the beetle rectal complex. Significance StatementBeetles are the largest group of insects, inhabiting a wide range of habitats on earth. Unique adaptations in overcoming water stress is critical to their success, yet the mechanisms underpinning this ability are unknown. Using genetics, electrophysiology, imaging and behavioral studies we show that a cation/H+ (NHA1) transporter is exclusively localized to specialized cell type, the leptophragmata, in the Malpighian tubules associated with the rectal complex. Ion transport functions of NHA1 in leptophragmata underpin the movement of water from the rectum, from where it would be destined for excretion, to the Malpighian tubule and then recycled back to the body. This water recovery capability of rectal complex is essential for maintaining systemic water balance in beetles. This work provides the first insight into to the molecular architecture of one of most powerful water-conservation mechanisms in biology, and provides an important clue to the ecological and evolutionary success of the beetles.

systems biology↗

bioRxiv2022

A gut-derived hormone switches dietary preference after mating in Drosophila

Animals must adapt their dietary choices to meet their nutritional needs. How these needs are detected and translated into nutrient-specific appetites that drive food-choice behaviors is poorly defined. Here, we show that the enteroendocrine cells (EECs) of the adult female Drosophila midgut sense nutrients and in response release neuropeptide F (NPF), an ortholog of mammalian NPY-family gut-brain hormones. Gut-derived NPF acts via effects on glucagon-like adipokinetic hormone (AKH) signaling to induce sugar satiety and to drive hunger for protein-rich food, and on adipose tissue to promote storage of ingested nutrients. Suppression of gut NPF leads to overconsumption of dietary sugar while decreasing intake of protein-rich yeast. Furthermore, we show a female-specific function of gut-derived NPF in the suppression of AKH signaling after mating. This induces a dietary switch that promotes preference for protein-containing food to support reproduction. Together, our findings suggest that the gut NPF-AKH axis regulates appetite that drives specific food choices to ensure homeostatic consumption of nutrients, providing insight into the hormonal mechanisms that underlie nutrient-specific hungers.

animal behavior and cognition↗

bioRxiv2021

Biomechanical characteristics of scapula and glenohumeral movements during pitching motion in injury-prone college baseball pitchers

Coordination of glenohumeral and scapular movements plays an important role in the injury prevention of baseball pitchers. However, there is no objective data establishing the direct relationship between pitching injuries and associated glenohumeral and scapular movements. Therefore, the objectives of the present study were to demonstrate biomechanical differences in scapular and glenohumeral movements during pitching between injury-prone pitchers and healthy college baseball pitchers. Thirty collegiate baseball pitchers were classified into two groups according to their injury status: injury-prone group (N=15, 20.7{+/-}1.4 years, 180.1{+/-}6.5 cm, 78.9{+/-}5.4 kg) and control group (N=15, 20.9{+/-}1.1 years, 177.1{+/-}6.6 cm, 72.3{+/-}6.7 kg). We obtained the pitching motion data using the three-dimensional motion analysis technique with four high-speed cameras. The horizontal abduction angles of the glenohumeral joint during cocking and acceleration phases were significantly greater in injury-prone pitchers [19.0{degrees} (95% CI: 14.4-23.6) at foot contact, -4.0{degrees} (95% CI: -7.7 to -0.2) at maximum external rotation (MER), and -0.3{degrees} (95% CI: -4.8 to -4.2) at ball release] than in healthy controls [11.7 {degrees}(95%CI:7.1 to 16.3) at foot contact, -10.0{degrees}(95%CI: -13.7 to -6.3) at MER, and -6.9{degrees}(95%CI: -11.4 to -2.4)](p<0.01). In addition, the external rotation angle (ER) of the scapula at MER was significantly greater in the injury-prone group [-0.1{degrees} (95% CI: -5.0 to 4.8)] than in the control group [-12.3{degrees} (95% CI: -17.2 to -7.4)] (p<0.01), but there was no difference in the scapular ER during foot contact between the two groups. These results suggests that injury-prone pitchers have less internal rotation of the scapula and more horizontal abduction of the glenohumeral joint during cocking and acceleration phases. Therefore, sports medicine practitioners may need to pay more attention to coordination of scapular and glenohumeral movements during the cocking and acceleration phases of pitching for prevention of shoulder injuries.

physiology↗

bioRxiv2021

Repeated translocation of a supergene underlying rapid sex chromosome turnover in Takifugu fish

Recent studies have revealed a surprising diversity of sex chromosomes in vertebrates. However, the detailed mechanism of their turnover is still elusive. To understand this process, it is necessary to compare closely related species in terms of sex-determining genes and the chromosomes harboring them. Here, we explored the genus Takifugu, in which one strong candidate sex-determining gene, Amhr2, has been identified. To trace the processes involved in transitions in the sex determination system in this genus, we studied 12 species and found that while the Amhr2 locus likely determines sex in the majority of Takifugu species, three species have acquired sex-determining loci at different chromosomal locations. Nevertheless, the generation of genome assemblies for the three species revealed that they share a portion of the male-specific supergene that contains a candidate sex-determining gene, GsdfY, along with genes that potentially play a role in male fitness. The shared supergene span approximately 100 kb and are flanked by two duplicated regions characterized by CACTA transposable elements. These results suggest that the shared supergene has taken over the role of sex-determining locus from Amhr2 in lineages leading to the three species, and repeated translocations of the supergene underlie the turnover of sex chromosomes in these lineages. These findings highlight the underestimated role of a mobile supergene in the turnover of sex chromosomes in vertebrates. SignificanceAlthough turnover of sex chromosomes is very common in many vertebrate lineages, the transition process is still elusive. We studied the sex-determining region (SDR) of 12 congeneric fish species. We found that while nine species retained their ancestral SDR, three species had acquired derived SDRs. Although the derived SDRs resided in three different chromosomes, they harbored a shared supergene flanked by two putative transposable elements. The results highlight the underestimated role of a mobile supergene in turnover of sex chromosomes in vertebrates.

genomics↗

bioRxiv2021

Co-option of local and systemic immune responses by the hormonal signalling system triggering metamorphosis

Insect metamorphosis is regulated by the production, secretion and degradation of two peripheral hormones: 20-hydroxyecdysone (ecdysone) and juvenile hormone (JH). In addition to their roles in developmental regulation, increasing evidence suggests that these hormones are involved in innate immunity processes, such as phagocytosis and the induction of antimicrobial peptide (AMP) production. AMP regulation includes systemic responses as well as local responses at surface epithelia that contact with the external environment. At pupariation, Drosophila melanogaster increases dramatically the expression of three AMP genes, drosomycin (drs), drosomycin-like 2 (drsl2) and drosomycin-like 5 (drsl5). We show that the systemic action of drs at pupariation is dependent on ecdysone signalling in the fat body and operates via the ecdysone downstream target, Broad-Z4. In parallel, ecdysone also regulates local responses, specifically through the activation of drsl2 expression in the gut. Finally, we confirm the relevance of this ecdysone dependent AMP expression for the control of bacterial persistence by showing that flies lacking drs expression in the fat body have higher bacterial persistence over metamorphosis. Together, our data emphasize the importance of the association between ecdysone signalling and immunity using in vivo studies and establish a new role for ecdysone at pupariation, which impacts developmental success by regulating the immune system in a stage-dependent manner. We speculate that this co-option of immune effectors by the hormonal system may constitute a pre-emptive mechanism to control bacterial numbers in the pupa at the core of metamorphosis evolution.

developmental biology↗

bioRxiv2021

Single-cell RNA-seq analysis reveals penaeid shrimp hemocyte subpopulations and cell differentiation process

Crustacean aquaculture is expected to be a major source of fishery commodities in the near future. Hemocytes are key players of the immune system in shrimps; however, their classification, maturation, and differentiation are still under debate. To date, only discrete and inconsistent information on the classification of shrimp hemocytes has been reported, showing that the morphological characteristics are not sufficient to resolve their actual roles. Our present study using single-cell RNA sequencing, revealed nine types of hemocytes of Marsupenaeus japonicus based on their transcriptional profiles. We identified markers of each subpopulation and the differentiation pathways involved in their maturation. We also discovered cell growth factors that might play crucial roles in hemocyte differentiation. Different immune roles among these subpopulations were suggested from the analysis of differentially expressed immune-related genes. These results provide a unified classification of shrimp hemocytes, which improves the understanding of its immune system.

cell biology↗

bioRxiv2020

Ecdysone coordinates plastic growth with robust pattern in the developing wing

Animals develop in unpredictable, variable environments. In response to environmental change some aspects of development adjust to generate plastic phenotypes. Other aspects of development, however, are buffered against environmental change to produce robust phenotypes. How organ development is coordinated to accommodate both plastic and robust developmental responses is poorly understood. Here, we demonstrate that the steroid hormone ecdysone coordinates both plasticity of organ size and robustness of organ pattern in the developing wings of the fruit fly Drosophila melanogaster. Using fed and starved larvae that lack prothoracic glands, which synthesise ecdysone, we show that nutrition regulates growth both via ecdysone and via an ecdysone-independent mechanism, while nutrition regulates patterning only via ecdysone. We then demonstrate that growth shows a graded response to ecdysone concentration, while patterning shows a threshold response. Collectively, these data support a model where nutritionally-regulated ecdysone fluctuations confer plasticity by regulating disc growth in response to basal ecdysone levels, and confers robustness by initiating patterning only once ecdysone peaks exceeds a threshold concentration. This could represent a generalizable mechanism through which hormones coordinate plastic growth with robust patterning in the face of environmental change.

developmental biology↗

bioRxiv2020

The gut hormone Allatostatin C regulates food intake and metabolic homeostasis under nutrient stress

The intestine is a central regulator of metabolic homeostasis. Dietary inputs are absorbed through the gut, which senses their nutritional value and relays hormonal information to other organs to coordinate systemic energy balance. However, the specific gut hormones that communicate energy availability to target organs to induce appropriate metabolic and behavioral responses are poorly defined. Here we show that the enteroendocrine cells (EECs) of the Drosophila gut sense nutrient stress via the intracellular TOR pathway, and in response secrete the peptide hormone allatostatin C (AstC). Gut-derived AstC induces secretion of glucagon-like adipokinetic hormone (AKH) via its receptor AstC-R2, a homolog of mammalian somatostatin receptors, to coordinate food intake and energy mobilization. Loss of gut AstC or its receptor in the AKH-producing cells impairs lipid and sugar mobilization during fasting, leading to hypoglycemia. Our findings illustrate a nutrient-responsive endocrine mechanism that maintains energy homeostasis under nutrient-stress conditions, a function that is essential to health and whose failure can lead to metabolic disorders.

physiology↗

bioRxiv2020

A Unique Renal Architecture in Tribolium castaneum Informs the Evolutionary Origins of Systemic Osmoregulation in Beetles

Maintaining internal salt and water balance in response to fluctuating external conditions is essential for animal survival. This is particularly true for insects as their high surface-to-volume ratio makes them highly susceptible to osmotic stress. However, the cellular and hormonal mechanisms that mediate the systemic control of osmotic homeostasis in beetles (Coleoptera), the largest group of insects, remain largely unidentified. Here, we demonstrate that eight neurons in the brain of the red flour beetle Tribolium castaneum respond to internal changes in osmolality by releasing diuretic hormone (DH) 37 and DH47 - homologues of vertebrate corticotropinreleasing factor (CRF) hormones - to control systemic water balance. Knockdown of the gene encoding the two hormones (Urinate, Urn8) reduces renal secretion and restricts organismal fluid loss, whereas injection of DH37 or DH47 reverses these phenotypes. We further identify a novel CRF-like receptor, Urinate Receptor (Urn8R), which is exclusively expressed in a unique secondary cell (SC) in the beetle renal organs, as underlying this response. Activation of Urn8R increases K+ secretion specifically through SCs, creating a lumen-positive transepithelial potential that drives fluid secretion. Together, these data show that beetle renal organs operate by fundamentally different mechanism than those of other insects. Finally, we adopt a fluorescent labelling strategy to identify the evolutionary origin of this unusual renal architecture within the large Order of Coleoptera. Our work thus uncovers an important homeostatic program that is key to maintaining osmotic control in beetles, which evolved in parallel to the radiation of the higher beetle families. Significance StatementBeetles are the most diverse animal group on the planet. Their evolutionary success suggests unique physiological adaptations in overcoming water stress, yet the mechanisms underlying this ability are unknown. Here we use molecular genetic, electrophysiology and behavioral studies to show that a group of brain neurons responds to osmotic disturbances by releasing diuretic hormones that regulate salt and water balance. These hormones bind to their receptor exclusively localized to a unique secondary cell in the renal organs to modulate fluid secretion and organismal water loss. This renal architecture, common to all higher beetle families, is novel within the insects, and provides an important clue to the evolutionary success of the beetles in colonizing an astounding range of habitats on Earth.

physiology↗