The V-type H <sup>+</sup> -ATPase is targeted in anti-diuretic hormone control of the Malpighian ‘renal’ tubules
Bibliographic record
Abstract
Abstract Like other insects, secretion by mosquito Malpighian tubules (MTs) is driven by the V-type H + -ATPase (VA) localized in the apical membrane of principal cells. In Aedes aegypti , the anti-diuretic neurohormone CAPA inhibits secretion by MTs stimulated by select diuretic hormones; however, the cellular effectors of this inhibitory signaling cascade remain unclear. Herein, we demonstrate that the VA inhibitor bafilomycin selectively inhibits serotonin (5HT)- and calcitonin-related diuretic hormone (DH 31 )-stimulated secretion. VA activity increases in DH 31 -treated MTs, whereas CAPA abolishes this increase through a NOS/cGMP/PKG signaling pathway. A critical feature of VA activation involves the reversible association of the cytosolic (V 1 ) and membrane (V o ) complexes. Indeed, higher V 1 protein abundance was found in membrane fractions of DH 31 -treated MTs whereas CAPA significantly decreased V 1 abundance in membrane fractions while increasing it in cytosolic fractions. V 1 immunolocalization was observed strictly in the apical membrane of DH 31 treated MTs whereas immunoreactivity was dispersed following CAPA treatment. VA complexes colocalized apically in female MTs shortly after a blood-meal consistent with the peak and post-peak phases of diuresis. Comparatively, V 1 immunoreactivity in MTs was more dispersed and did not colocalize with the V o complex in the apical membrane at 3 hours post blood-meal, representing a timepoint after the late phase of diuresis has concluded. Therefore, CAPA inhibition of MTs involves reducing VA activity and promotes complex dissociation hindering secretion. Collectively, these findings reveal a key target in hormone-mediated inhibition of MTs countering diuresis that provides a deeper understanding of this critical physiological process necessary for hydromineral balance. Significance Statement The V-type H + ATPase (VA), or proton pump, provides the driving force for transepithelial ion and fluid secretion in insect Malpighian tubules (MTs). While studies have shown diuretic stimulation activates various signaling pathways, including cAMP and downstream effectors promoting increased VA activity, our understanding of anti-diuretic signaling and its potential regulation of the VA remains rudimentary. Herein, we show that CAPA neuropeptide acts through the NOS/cGMP/PKG pathway to inhibit DH 31 -stimulated VA activity, supporting the notion that the anti-diuretic regulation is achieved through dissociation of the VA complexes. These results demonstrate a critical role of VA inhibition and trafficking necessary for anti-diuretic signaling and advances our understanding of the complex neuroendocrine control of the MTs in this important human disease-vector mosquito.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".