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

Sajadi, Farwa; Paluzzi, Jean‐Paul

doi:10.1101/2022.02.13.480270

Cited by 3 publications

(3 citation statements)

References 108 publications

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“…For instance, in the locust Schistocerca gregaria , ITPa but not ITPL promotes ion and water reabsorption across the hindgut (Audsley et al ., 1992a, Audsley et al ., 1992b, King et al ., 1999, Wang et al ., 2000), thereby promoting anti-diuresis. Previous experiments have shown that the MTs are also targeted by anti-diuretic hormones: CAPA neuropeptides inhibit diuresis in some insects including Drosophila via direct hormonal actions on the renal tubules (Paluzzi et al ., 2008, MacMillan et al ., 2018, Sajadi et al ., 2020, Sajadi et al ., 2023). Given the expression of Gyc76C, a putative ITP receptor, in both the hindgut and renal tubules, ITP could modulate osmotic and/or ionic homeostasis by targeting these two excretory organs.…”

Section: Resultsmentioning

confidence: 99%

Anti-diuretic hormone ITP signals via a guanylate cyclase receptor to modulate systemic homeostasis inDrosophila

Gera,

Agard,

Nave

et al. 2024

Preprint

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Insects have evolved a variety of neurohormones that enable them to maintain their nutrient and osmotic homeostasis. While the identities and functions of various insect metabolic and diuretic hormones have been well-established, the characterization of an anti-diuretic signaling system that is conserved across most insects is still lacking. To address this, here we characterized the ion transport peptide (ITP) signaling system inDrosophila. TheDrosophila ITPgene encodes five transcript variants which generate three different peptide isoforms: ITP amidated (ITPa) and two ITP-like (ITPL1 and ITPL2) isoforms. Using a combination of anatomical mapping and single-cell transcriptome analyses, we comprehensively characterized the expression of all three ITP isoforms in the nervous system and peripheral tissues. Our analyses reveal widespread expression of ITP isoforms. Moreover, we show that ITPa is released during dehydration and recombinantDrosophilaITPa inhibits diuretic peptide-induced renal tubule secretionex vivo, thus confirming its role as an anti-diuretic hormone. Using a phylogenetic-driven approach and theex vivosecretion assay, we identified and functionally characterized Gyc76C, a membrane guanylate cyclase, as an elusiveDrosophilaITPa receptor. Thus, knockdown of Gyc76C in renal tubules abolishes the inhibitory effect of ITPa on diuretic hormone secretion. Extensive anatomical mapping of Gyc76C reveals that it is highly expressed in larval and adult tissues associated with osmoregulation (renal tubules and rectum) and metabolic homeostasis (fat body). Consistent with this expression, knockdown of Gyc76C in renal tubules impacts tolerance to osmotic and ionic stresses, whereas knockdown specifically in the fat body impacts feeding, nutrient homeostasis and associated behaviors. We also complement receptor knockdown experiments with ITPa overexpression in ITP neurons. Interestingly, ITPa-Gyc76C pathways deciphered here are reminiscent of the atrial natriuretic peptide signaling in mammals. Lastly, we utilized connectomics and single-cell transcriptomics to identify synaptic and paracrine pathways upstream and downstream of ITP-expressing neurons. Taken together, our systematic characterization of the ITP signaling establishes a tractable system to decipher how a small set of neurons integrates diverse inputs to orchestrate systemic homeostasis inDrosophila.

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Section: Resultsmentioning

confidence: 99%

Anti-diuretic hormone ITP signals via a guanylate cyclase receptor to modulate systemic homeostasis inDrosophila

Gera,

Agard,

Nave

et al. 2024

Preprint

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“…The MTs, which are functional analogs of vertebrate kidneys, are responsible for the formation of primary urine (Coast, 2007), driven by the V-type H + -ATPase (Wieczorek, 1992) that permits transport of Na + and K + cations across the membrane (Beyenbach, 2003) via a putative H + /cation exchanger (Wieczorek et al, 2009). The MTs are regulated by various diuretic and anti-diuretic hormones, which in A. aegypti includes the biogenic amine 5-hydroxytryptamine (5HT) (Clark and Bradley, 1998; Veenstra, 1988), DH 31 (Coast et al, 2005), DH 44 (Clark et al, 1998; Clark et al, 1998), kinin-like peptides (Lu et al, 2011; Pietrantonio et al, 2005) and CAPA that inhibits the activity of select diuretic hormones (Sajadi et al, 2018; Sajadi et al, 2020; Sajadi et al, 2023). The primary urine then enters the hindgut, where it is further modified through secretory and reabsorptive processes.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization, localization, and physiological roles of ITP and ITP-L in the mosquito,Aedes aegypti

Sajadi,

Paluzzi

2024

Preprint

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The insect ion transport peptide (ITP) and its alternatively spliced variant, ITP-like peptide (ITP-L), belong to the crustacean hyperglycemic hormone family of peptides and are widely conserved among insect species. While limited, studies have characterized the ITP/ITP-L signaling system within insects, and putative functions including regulation of ion and fluid transport, ovarian maturation, and thirst/excretion have been proposed. Herein, we aimed to molecularly investigate Itp and Itp-l expression profiles in the mosquito Aedes aegypti, examine peptide immunolocalization and distribution within the adult central nervous system, and elucidate physiological roles for these neuropeptides. Transcript expression profiles of both AedaeItp and AedaeItp-l revealed distinct enrichment patterns in adults, with AedaeItp expressed in the brain and AedaeItp-l expression predominantly within the abdominal ganglia. Immunohistochemical analysis within the central nervous system revealed expression of AedaeITP peptide in a number of cells in the brain and in the terminal ganglion. Comparatively, AedaeITP-L peptide was localized solely within the pre-terminal abdominal ganglia of the central nervous system. Interestingly, prolonged desiccation stress caused upregulation of AedaeItp and AedaeItp-l levels in adult mosquitoes, suggesting possible functional roles in water conservation and feeding-related activities. RNAi-mediated knockdown of AedaeItp caused an increase in urine excretion, while knockdown of both AedaeItp and AedaeItp-l reduced blood feeding and egg-laying in females as well as hindered egg viability, suggesting roles in reproductive physiology and behaviour. Altogether, this study identifies AedaeITP and AedaeITP-L as key pleiotropic hormones, regulating various critical physiological processes in the disease vector, A. aegypti.

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“…All study data are openly available at https://doi.org/10.5683/SP3/PADHU5 ( 83 ). All other data is included in the article and/or SI Appendix .…”

Section: Data Materials and Software Availabilitymentioning

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

Cited by 3 publications

References 108 publications

Anti-diuretic hormone ITP signals via a guanylate cyclase receptor to modulate systemic homeostasis inDrosophila

Anti-diuretic hormone ITP signals via a guanylate cyclase receptor to modulate systemic homeostasis inDrosophila

Molecular characterization, localization, and physiological roles of ITP and ITP-L in the mosquito,Aedes aegypti

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

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

Cited by 3 publications

References 108 publications

Anti-diuretic hormone ITP signals via a guanylate cyclase receptor to modulate systemic homeostasis inDrosophila

Anti-diuretic hormone ITP signals via a guanylate cyclase receptor to modulate systemic homeostasis inDrosophila

Molecular characterization, localization, and physiological roles of ITP and ITP-L in the mosquito,Aedes aegypti

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

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

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