Hormonal regulation and functional role of the “renal” tubules in the disease vector, Aedes aegypti

Sajadi, Farwa; Paluzzi, Jean‐Paul

doi:10.1016/bs.vh.2021.06.007

Cited by 5 publications

(9 citation statements)

References 151 publications

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“…Although the endogenous 5HT receptor expressed within the A. aegypti MTs necessary for diuretic activity remains elusive, in the kissing bug, Rhodnius prolixus , both cAMP and Ca 2+ have been shown to initiate diuresis in response to 5HT ( 52 ), which might explain the partial inhibitory response of Aedae CAPA-1 inhibition on 5HT-stimulated tubules as Ca 2+ -mediated diuresis is independent of the VA ( 39 ). Notably, the anticipated 5HT type 2 receptor subtype expressed in the principal cells of the MTs is predicted to couple through a Gq/11 signaling mechanism ( 53 ) and likely excludes the type 7 Gs-coupled receptor localized to tracheolar cells associated with the MTs ( 54 , 55 ) as well as the type 1 Gi-coupled receptor localized to principal cells in larval stage mosquitoes ( 56 ).…”

Section: Discussionmentioning

confidence: 99%

The V-type H ⁺ -ATPase is targeted in antidiuretic hormone control of the Malpighian “renal” tubules

Sajadi,

Vergara-Martínez,

Paluzzi

2023

Proc. Natl. Acad. Sci. U.S.A.

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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 antidiuretic 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 postpeak 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 h post blood meal, representing a time point 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.

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Section: Discussionmentioning

confidence: 99%

The V-type H ⁺ -ATPase is targeted in antidiuretic hormone control of the Malpighian “renal” tubules

Sajadi,

Vergara-Martínez,

Paluzzi

2023

Proc. Natl. Acad. Sci. U.S.A.

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“…The blood is rich in nutrients that mosquitoes must absorb to ensure successful egg production [ 73 ]. In addition, it is essential for the mosquito to quickly excrete toxic elements, such as heme groups (reactive species that can induce oxidative stress) and maintain salt and water homeostasis [ 74 , 75 ]. The midgut, MTs, and ovaries are major tissues involved in the above processes following a blood meal [ 76 ].…”

Section: Discussionmentioning

confidence: 99%

Octopamine and tyramine signalling in Aedes aegypti: Molecular characterization and insight into potential physiological roles

et al. 2023

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In insects, the biogenic amines octopamine (OA) and tyramine (TA) are involved in controlling several physiological and behavioural processes. OA and TA act as neurotransmitters, neuromodulators or neurohormones, performing their functions by binding to specific receptors belonging to the G protein-coupled receptor (GPCR) superfamily. OA and TA along with their receptors are involved in reproduction, smell perception, metabolism, and homeostasis. Moreover, OA and TA receptors are targets for insecticides and antiparasitic agents, such as the formamidine Amitraz. In the dengue and yellow fever vector, Aedes aegypti, limited research has been reported on their OA or TA receptors. Here, we identify and molecularly characterize the OA and TA receptors in A. aegypti. Bioinformatic tools were used to identify four OA and three TA receptors in the genome of A. aegypti. The seven receptors are expressed in all developmental stages of A. aegypti; however, their highest transcript abundance is observed in the adult. Among several adult A. aegypti tissues examined, including the central nervous system, antennae and rostrum, midgut, Malpighian tubules, ovaries, and testes, the type 2 TA receptor (TAR2) transcript is most abundant in the ovaries and the type 3 TA receptor (TAR3) is enriched in the Malpighian tubules, leading us to propose putative roles for these receptors in reproduction and diuresis, respectively. Furthermore, a blood meal influenced OA and TA receptor transcript expression patterns in adult female tissues at several time points post blood meal, suggesting these receptors may play key physiological roles associated with feeding. To better understand OA and TA signalling in A. aegypti, the transcript expression profiles of key enzymes in their biosynthetic pathway, namely tyrosine decarboxylase (Tdc) and tyramine β-hydroxylase (Tβh), were examined in developmental stages, adult tissues, and brains from blood-fed females. These findings provide information for better understanding the physiological roles of OA, TA, and their receptors in A. aegypti, and additionally, may help in the development of novel strategies for the control of these human disease vectors.

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“…Although the endogenous 5HT receptor expressed within the A. aegypti MTs necessary for diuretic activity remains elusive, in the kissing bug, Rhodnius prolixus , both cAMP and Ca 2+ have been shown to initiate diuresis in response to 5HT (51), which could explain the partial inhibitory response of Aedae CAPA-1 inhibition on 5HT-stimulated tubules as Ca 2+ - mediated diuresis is independent of the VA (38). Notably, the anticipated 5HT type 2 receptor subtype expressed in the principal cells of the MTs is predicted to couple through a Gq/11 signaling mechanism (52) and likely excludes the type 7 Gs-coupled receptor localized to tracheolar cells associated with the MTs (53, 54) as well as the type 1 Gi-coupled receptor localized to principal cells in larval stage mosquitoes (55).…”

Section: Discussionmentioning

confidence: 99%

The V-type H⁺-ATPase is targeted in anti-diuretic hormone control of the Malpighian ‘renal’ tubules

Sajadi

Paluzzi

2022

Preprint

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Like other insects, secretion by mosquito MTs is driven by the V-type H+-ATPase (VA), which is densely packed in the apical membrane of principal cells. The anti-diuretic neurohormone CAPA inhibits tubule secretion stimulated by select diuretic hormones; however, the cellular effectors of this inhibitory signaling cascade remain unclear. Herein, we show that the VA inhibitor bafilomycin selectively inhibits serotonin (5HT)- and calcitonin-related diuretic hormone (DH31)-stimulated secretion. VA activity increases in DH31-treated MTs, whereas CAPA abolishes this increase. A critical feature of VA activation involves the reversible association of the cytosolic (V1) and membrane (Vo) complexes and results revealed higher V1 protein abundance in membrane fractions of DH31-treated MTs whereas CAPA significantly decreased V1 protein abundance in membrane fractions while increasing it in cytosolic fractions. Immunolocalization of V1 was observed strictly in the apical membrane of MTs treated with DH31 alone whereas immunoreactivity was dispersed following CAPA treatment. Elevated levels of cGMP in CAPA-treated MTs suggests activation of a phosphodiesterase (PDE), resulting in decreased levels of DH31-stimulated cAMP. Therefore, CAPA inhibition of MTs involves reducing VA activity and promotes complex dissociation hindering secretion. Collectively, these findings reveal a key target necessary for hormone-mediated inhibition of MTs required in countering diuresis providing a deeper understanding of this critical physiological process.Significance StatementThe V-type H+-ATPase (VA) proton pump, provides the driving force for transepithelial ion and fluid secretion in insect Malpighian tubules (MTs). While studies have shown that diuretic stimulation activates various signaling pathways that culminate with increased VA activity, our understanding of anti-diuretic signaling and its potential regulation involving the VA remains rudimentary. Here we show that a CAPA neuropeptide acts through the NOS/cGMP/PKG pathway that inhibits VA activity, supporting the notion that anti-diuretic regulation is mediated through reversible dissociation of the VA complexes. Our results demonstrate a critical role of VA inhibition and trafficking necessary for anti-diuretic signaling, advancing our understanding of the complex neuroendocrine regulatory mechanisms of the MTs in an important human disease vector mosquito.

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Hormonal regulation and functional role of the “renal” tubules in the disease vector, Aedes aegypti

Cited by 5 publications

References 151 publications

The V-type H ⁺ -ATPase is targeted in antidiuretic hormone control of the Malpighian “renal” tubules

The V-type H ⁺ -ATPase is targeted in antidiuretic hormone control of the Malpighian “renal” tubules

Octopamine and tyramine signalling in Aedes aegypti: Molecular characterization and insight into potential physiological roles

The V-type H⁺-ATPase is targeted in anti-diuretic hormone control of the Malpighian ‘renal’ tubules

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Hormonal regulation and functional role of the “renal” tubules in the disease vector, Aedes aegypti

Cited by 5 publications

References 151 publications

The V-type H + -ATPase is targeted in antidiuretic hormone control of the Malpighian “renal” tubules

The V-type H + -ATPase is targeted in antidiuretic hormone control of the Malpighian “renal” tubules

Octopamine and tyramine signalling in Aedes aegypti: Molecular characterization and insight into potential physiological roles

The V-type H+-ATPase is targeted in anti-diuretic hormone control of the Malpighian ‘renal’ tubules

Contact Info

Product

Resources

About

The V-type H ⁺ -ATPase is targeted in antidiuretic hormone control of the Malpighian “renal” tubules

The V-type H ⁺ -ATPase is targeted in antidiuretic hormone control of the Malpighian “renal” tubules

The V-type H⁺-ATPase is targeted in anti-diuretic hormone control of the Malpighian ‘renal’ tubules