Elucidating the Anti‐Diuretic Hormone Signalling System of CAPA Neuropeptides in the Disease Vector Mosquito, <i>Aedes aegypti</i>
Bibliographic record
Abstract
Blood‐feeding insects, including female Aedes aegypti mosquitoes, face the challenge of excess water and ion intake after a blood meal. To cope with this, insects have a highly active excretory system that includes the Malpighian ‘renal’ tubules (MTs), which are under rigorous control by several neuroendocrine factors. While endocrine regulation has been extensively studied in insects, most research has focused on the effects of diuretic hormones with limited study on anti‐diuretic hormones. Insect CAPA neuropeptides are produced in the central nervous system and are evolutionarily related to the vertebrate neuromedinU peptides. While CAPA peptides elicit distinct responses in different insect species, their activity on stimulated MTs in the adult A. aegypti remained unknown. Given the CAPA receptor is highly enriched in insect MTs, the objectives of this study were to examine the effects of a CAPA peptide on adult female MTs stimulated with various diuretic factors. The effect of endocrine factors on fluid secretion rate was measured using an in vitro bioassay where CAPA was found to inhibit secretion of MTs stimulated by select diuretic factors, 5‐HT and DH 31 , while having no effect on other diuretic factors, including kinin‐related and corticotropin releasing factor‐related (CRF) peptides. Although CAPA elicits strong anti‐diuretic activity, it does not influence the relative proportions of cations transported by adult MTs, thus maintaining the kaliuretic activity of 5‐HT and the natriuretic activity of DH 31 . Notably, the inhibitory effect of CAPA was abolished by knocking down the receptor using RNAi, verifying its critical role in anti‐diuresis. To investigate the signalling cascade mediating this anti‐diuretic effect, the second messenger cGMP was tested on adult MTs revealing that both 5‐HT and DH 31 –stimulated secretion is strongly inhibited by cGMP, similar to effects seen with CAPA. Pharmacological inhibition of PKG/NOS signalling abolishes the anti‐diuretic activity of CAPA, confirming the role of cGMP/PKG/NOS in the CAPA signalling pathway. Furthermore, MTs treated with bafilomycin, a V‐type H + ‐ATPase inhibitor, was found to inhibit fluid secretion stimulated by 5‐HT and DH 31 , while having no inhibitory action on CRF‐stimulated MTs. Additionally, alkalization of the secreted fluid in response to CAPA suggests inhibition of the apical V‐type H + ‐ATPase, which may lead to constrained entry of cations (Na + and K + ) across the apical membrane of the MTs. A. aegypti mosquitoes are vectors of a variety of pathogens leading to diseases including Dengue fever and Zika virus. In this study, the importance of hormonal regulation of the MTs is demonstrated, analyzing the importance of both diuretic and anti‐diuretic hormones. Given the central importance of the MTs in insect biology, these insights will be useful considering the need to develop novel strategies or compounds which more specifically and efficiently reduce the burden of insect disease vectors. Support or Funding Information Supported by an NSERC Discovery Grant (JPP), Petro Canada Young Innovator Award (JPP), Ontario Ministry of Research & Innovation Early Researcher Award (JPP), NSERC Canada Graduate Scholarship (FS), Vernon Oliver Stong Graduate Scholarship in Science (FS), and The Carswell Scholarships in the Faculty of Science (FS)
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".