scholarly journals A neuroendocrine pathway modulating osmotic stress in Drosophila

PLoS Genetics ◽  
2021 ◽  
Vol 17 (3) ◽  
pp. e1009425
Author(s):  
Meet Zandawala ◽  
Thomas Nguyen ◽  
Marta Balanyà Segura ◽  
Helena A. D. Johard ◽  
Mirjam Amcoff ◽  
...  
Keyword(s):  
Stress Responses ◽  
Fat Body ◽  
Ion Homeostasis ◽  
Metabolic Stress ◽  
Neurosecretory Cells ◽  
Chill Coma ◽  
Ionic Stress ◽  
Physiological Homeostasis ◽  
Simultaneous Activation ◽  
Regulatory Functions

Environmental factors challenge the physiological homeostasis in animals, thereby evoking stress responses. Various mechanisms have evolved to counter stress at the organism level, including regulation by neuropeptides. In recent years, much progress has been made on the mechanisms and neuropeptides that regulate responses to metabolic/nutritional stress, as well as those involved in countering osmotic and ionic stresses. Here, we identified a peptidergic pathway that links these types of regulatory functions. We uncover the neuropeptide Corazonin (Crz), previously implicated in responses to metabolic stress, as a neuroendocrine factor that inhibits the release of a diuretic hormone, CAPA, and thereby modulates the tolerance to osmotic and ionic stress. Both knockdown of Crz and acute injections of Crz peptide impact desiccation tolerance and recovery from chill-coma. Mapping of the Crz receptor (CrzR) expression identified three pairs of Capa-expressing neurons (Va neurons) in the ventral nerve cord that mediate these effects of Crz. We show that Crz acts to restore water/ion homeostasis by inhibiting release of CAPA neuropeptides via inhibition of cAMP production in Va neurons. Knockdown of CrzR in Va neurons affects CAPA signaling, and consequently increases tolerance for desiccation, ionic stress and starvation, but delays chill-coma recovery. Optogenetic activation of Va neurons stimulates excretion and simultaneous activation of Crz and CAPA-expressing neurons reduces this response, supporting the inhibitory action of Crz. Thus, Crz inhibits Va neurons to maintain osmotic and ionic homeostasis, which in turn affects stress tolerance. Earlier work demonstrated that systemic Crz signaling restores nutrient levels by promoting food search and feeding. Here we additionally propose that Crz signaling also ensures osmotic homeostasis by inhibiting release of CAPA neuropeptides and suppressing diuresis. Thus, Crz ameliorates stress-associated physiology through systemic modulation of both peptidergic neurosecretory cells and the fat body in Drosophila.

scholarly journals A neuroendocrine pathway modulating osmotic stress in Drosophila

2019 ◽  
Author(s):  
Meet Zandawala ◽  
Thomas Nguyen ◽  
Marta Balanyà Segura ◽  
Helena A. D. Johard ◽  
Mirjam Amcoff ◽  
...  
Keyword(s):  
Osmotic Stress ◽  
Stress Responses ◽  
Desiccation Tolerance ◽  
Fat Body ◽  
Neurosecretory Cells ◽  
Malpighian Tubules ◽  
Ionic Balance ◽  
Chill Coma ◽  
Energy Mobilization ◽  
Neuroendocrine Axis

AbstractEnvironmental factors challenge the physiological homeostasis in animals, thereby evoking stress responses. Various mechanisms have evolved to counter stress at the organism level, including regulation by neuropeptides. Although much progress has been made on the mechanisms and neuropeptides influencing nutritional stress, relatively little is known about the factors and pathways regulating osmotic and ionic stresses. Here, we uncover the neuropeptide Corazonin (Crz) as a neuroendocrine factor that modulates the release of an osmoregulatory peptide, CAPA, to regulate tolerance to osmotic and ionic stress. Both knockdown of Crz and acute injections of Crz peptide impact desiccation tolerance and recovery from chill-coma. Comprehensive mapping of the Crz receptor (CrzR) expression identified three pairs of Capa-expressing neurons (Va neurons) in the ventral nerve cord that mediate these effects of Crz. We further show that Crz is released during dry starvation (desiccation) and acts to restore homeostasis by inhibiting CAPA release via inhibition of cAMP production in Va neurons. Finally, knockdown of CrzR in Va neurons also affects CAPA release, and consequently influences desiccation tolerance and chill-coma recovery, considered proxies for diuretic state. Thus, Crz modulates Va neurons to maintain osmotic and ionic homeostasis, which in turn influences stress tolerance. Taken together with our previous work showing that systemic Crz signaling acts to restore nutrients levels by promoting food search and feeding, we propose that Crz signaling also ensures osmotic homeostasis by inhibiting the anti-diuretic CAPA peptides. Thus, Crz ameliorates stress-associated physiology through systemic modulation of both peptidergic neurosecretory cells and the fat body in Drosophila.Author summaryInsects are among the largest groups of animals and have adapted to inhabit almost all environments on Earth. Their success in surviving extreme conditions stems largely from their ability to withstand environmental stress, such as desiccation and cold. However, the neural mechanisms that are responsible for coordinating responses to counter these stresses are largely unknown. To address this, we delineate a neuroendocrine axis utilizing the neuropeptides Corazonin (Crz) and CAPA, that coordinate responses to metabolic and osmotic stress. We show that Crz modulates the release of an anti-diuretic peptide, CAPA from a set of neurosecretory cells. CAPA in turn influences osmotic and ionic balance via actions on the Malpighian tubules (the insect analogs of the kidney) and the intestine. Taken together with earlier work, our data suggest that Crz acts to restore metabolic homeostasis at starvation and as a cosenquence of energy mobilization and ensuing metabolic water production, fluid balance needs to be adjusted and therefore CAPA release is inhibited. Hence, this work provides a mechanistic understanding of the neuroendocrine mitigation of metabolic and osmotic stress by two peptide systems.

scholarly journals Metabolic Stress Responses in Drosophila Are Modulated by Brain Neurosecretory Cells That Produce Multiple Neuropeptides

PLoS ONE ◽  
2010 ◽  
Vol 5 (7) ◽  
pp. e11480 ◽  
Author(s):  
Lily Kahsai ◽  
Neval Kapan ◽  
Heinrich Dircksen ◽  
Åsa M. E. Winther ◽  
Dick R. Nässel
Keyword(s):  
Stress Responses ◽  
Metabolic Stress ◽  
Neurosecretory Cells

scholarly journals Systemic corazonin signalling modulates stress responses and metabolism in Drosophila

Open Biology ◽  
2016 ◽  
Vol 6 (11) ◽  
pp. 160152 ◽  
Author(s):  
Olga I. Kubrak ◽  
Oleh V. Lushchak ◽  
Meet Zandawala ◽  
Dick R. Nässel
Keyword(s):  
Stress Responses ◽  
Fat Body ◽  
Metabolic Stress ◽  
Gonadotropin Releasing Hormone ◽  
Stress Physiology ◽  
Adipokinetic Hormone ◽  
Systemic Reactions ◽  
Energy Stores ◽  
And Oxidative Stress ◽  
Signalling Systems

Stress triggers cellular and systemic reactions in organisms to restore homeostasis. For instance, metabolic stress, experienced during starvation, elicits a hormonal response that reallocates resources to enable food search and readjustment of physiology. Mammalian gonadotropin-releasing hormone (GnRH) and its insect orthologue, adipokinetic hormone (AKH), are known for their roles in modulating stress-related behaviour. Here we show that corazonin (Crz), a peptide homologous to AKH/GnRH, also alters stress physiology in Drosophila . The Crz receptor (CrzR) is expressed in salivary glands and adipocytes of the liver-like fat body, and CrzR knockdown targeted simultaneously to both these tissues increases the fly's resistance to starvation, desiccation and oxidative stress, reduces feeding, alters expression of transcripts of Drosophila insulin-like peptides (DILPs), and affects gene expression in the fat body. Furthermore, in starved flies, CrzR-knockdown increases circulating and stored carbohydrates. Thus, our findings indicate that elevated systemic Crz signalling during stress coordinates increased food intake and diminished energy stores to regain metabolic homeostasis. Our study suggests that an ancient stress-peptide in Urbilateria evolved to give rise to present-day GnRH, AKH and Crz signalling systems.

scholarly journals Arabidopsis heat shock transcription factor HSFA7b positively mediates salt stress tolerance by binding to an E-box-like motif to regulate gene expression

2019 ◽  
Vol 70 (19) ◽  
pp. 5355-5374 ◽  
Author(s):  
Dandan Zang ◽  
Jingxin Wang ◽  
Xin Zhang ◽  
Zhujun Liu ◽  
Yucheng Wang
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Heat Shock ◽  
Salt Tolerance ◽  
Stress Responses ◽  
Ion Homeostasis ◽  
Cellulose Synthase ◽  
Regulate Gene Expression ◽  
E Box ◽  
Regulate Gene

Abstract Plant heat shock transcription factors (HSFs) are involved in heat and other abiotic stress responses. However, their functions in salt tolerance are little known. In this study, we characterized the function of a HSF from Arabidopsis, AtHSFA7b, in salt tolerance. AtHSFA7b is a nuclear protein with transactivation activity. ChIP-seq combined with an RNA-seq assay indicated that AtHSFA7b preferentially binds to a novel cis-acting element, termed the E-box-like motif, to regulate gene expression; it also binds to the heat shock element motif. Under salt conditions, AtHSFA7b regulates its target genes to mediate serial physiological changes, including maintaining cellular ion homeostasis, reducing water loss rate, decreasing reactive oxygen species accumulation, and adjusting osmotic potential, which ultimately leads to improved salt tolerance. Additionally, most cellulose synthase-like (CSL) and cellulose synthase (CESA) family genes were inhibited by AtHSFA7b; some of them were randomly selected for salt tolerance characterization, and they were mainly found to negatively modulate salt tolerance. By contrast, some transcription factors (TFs) were induced by AtHSFA7b; among them, we randomly identified six TFs that positively regulate salt tolerance. Thus, AtHSFA7b serves as a transactivator that positively mediates salinity tolerance mainly through binding to the E-box-like motif to regulate gene expression.

MondoA Drives B-ALL Malignancy through Enhanced Adaptation to Metabolic Stress

Blood ◽  
2021 ◽  
Author(s):  
Alexandra Sipol ◽  
Erik Hameister ◽  
Busheng Xue ◽  
Julia Hofstetter ◽  
Maxim Barenboim ◽  
...  
Keyword(s):  
Stress Responses ◽  
Lymphoblastic Leukemia ◽  
Metabolic Stress ◽  
Tca Cycle ◽  
Underlying Mechanism ◽  
Patient Data ◽  
Data Sets ◽  
Dependent Manner

Cancer cells are in most instances characterized by rapid proliferation and uncontrolled cell division. Hence, they must adapt to proliferation-induced metabolic stress through intrinsic or acquired anti-metabolic stress responses to maintain homeostasis and survival. One mechanism to achieve this is to reprogram gene expression in a metabolism-dependent manner. MondoA (also known as MLXIP), a member of the MYC interactome, has been described as an example of such a metabolic sensor. However, the role of MondoA in malignancy is not fully understood and the underlying mechanism in metabolic responses remains elusive. By assessing patient data sets we found that MondoA overexpression is associated with a worse survival in pediatric common acute lymphoblastic leukemia (B-ALL). Using CRISPR/Cas9 and RNA interference approaches, we observed that MondoA depletion reduces transformational capacity of B-ALL cells in vitro and dramatically inhibits malignant potential in an in vivo mouse model. Interestingly, reduced expression of MondoA in patient data sets correlated with enrichment in metabolic pathways. The loss of MondoA correlated with increased tricarboxylic acid (TCA) cycle activity. Mechanistically, MondoA senses metabolic stress in B-ALL cells by restricting oxidative phosphorylation through reduced PDH activity. Glutamine starvation conditions greatly enhance this effect and highlight the inability to mitigate metabolic stress upon loss of MondoA in B-ALL. Our findings give a novel insight into the function of MondoA in pediatric B-ALL and support the notion that MondoA inhibition in this entity offers a therapeutic opportunity and should be further explored.

scholarly journals Current Evidence for a Role of Neuropeptides in the Regulation of Autophagy

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Elisabetta Catalani ◽  
Clara De Palma ◽  
Cristiana Perrotta ◽  
Davide Cervia
Keyword(s):  
Molecular Mechanisms ◽  
Current Evidence ◽  
Pathological Conditions ◽  
Organ Systems ◽  
Intercellular Signalling ◽  
Physiological Homeostasis ◽  
Response To Stress ◽  
Autophagic Process ◽  
Regulatory Functions

Neuropeptides drive a wide diversity of biological actions and mediate multiple regulatory functions involving all organ systems. They modulate intercellular signalling in the central and peripheral nervous systems as well as the cross talk among nervous and endocrine systems. Indeed, neuropeptides can function as peptide hormones regulating physiological homeostasis (e.g., cognition, blood pressure, feeding behaviour, water balance, glucose metabolism, pain, and response to stress), neuroprotection, and immunomodulation. We aim here to describe the recent advances on the role exerted by neuropeptides in the control of autophagy and its molecular mechanisms since increasing evidence indicates that dysregulation of autophagic process is related to different pathological conditions, including neurodegeneration, metabolic disorders, and cancer.

Emerging roles of endoplasmic reticulum-resident selenoproteins in the regulation of cellular stress responses and the implications for metabolic disease

2018 ◽  
Vol 475 (6) ◽  
pp. 1037-1057 ◽  
Author(s):  
Alex B. Addinsall ◽  
Craig R. Wright ◽  
Sof Andrikopoulos ◽  
Chris van der Poel ◽  
Nicole Stupka
Keyword(s):  
Metabolic Disease ◽  
Endoplasmic Reticulum ◽  
Stress Responses ◽  
Cellular Stress ◽  
Metabolic Stress ◽  
Metabolic Dysfunction ◽  
Iodothyronine Deiodinase ◽  
Inflammatory Stress ◽  
Cellular Stress Responses

Chronic metabolic stress leads to cellular dysfunction, characterized by excessive reactive oxygen species, endoplasmic reticulum (ER) stress and inflammation, which has been implicated in the pathogenesis of obesity, type 2 diabetes and cardiovascular disease. The ER is gaining recognition as a key organelle in integrating cellular stress responses. ER homeostasis is tightly regulated by a complex antioxidant system, which includes the seven ER-resident selenoproteins — 15 kDa selenoprotein, type 2 iodothyronine deiodinase and selenoproteins S, N, K, M and T. Here, the findings from biochemical, cell-based and mouse studies investigating the function of ER-resident selenoproteins are reviewed. Human experimental and genetic studies are drawn upon to highlight the relevance of these selenoproteins to the pathogenesis of metabolic disease. ER-resident selenoproteins have discrete roles in the regulation of oxidative, ER and inflammatory stress responses, as well as intracellular calcium homeostasis. To date, only two of these ER-resident selenoproteins, selenoproteins S and N have been implicated in human disease. Nonetheless, the potential of all seven ER-resident selenoproteins to ameliorate metabolic dysfunction warrants further investigation.

Sign in / Sign up

Export Citation Format

Share Document