Abstract
Insect CAPA neuropeptides are homologs of mammalian neuromedin U and are known to influence ion and water balance by regulating the activity of the Malpighian ‘renal’ tubules (MTs). Several diuretic hormones are known to increase primary fluid and ion secretion by insect MTs and, in adult female mosquitoes, a calcitonin-related peptide (DH31) called mosquito natriuretic peptide, increases sodium secretion to compensate for the excess salt load acquired during blood-feeding. An endogenous mosquito anti-diuretic hormone was recently described, having potent inhibitory activity against select diuretic hormones, including DH31. Herein, we functionally deorphanized, both in vitro and in vivo, a mosquito anti-diuretic hormone receptor (AedaeADHr) with expression analysis indicating highest enrichment in the MTs where it is localized within principal cells. Characterization using a heterologous in vitro system demonstrated the receptor was highly sensitive to mosquito CAPA neuropeptides while in vivo, AedaeADHr knockdown abolished CAPA-induced anti-diuretic control of DH31-stimulated MTs. CAPA neuropeptides are produced within a pair of neurosecretory cells in each of the abdominal ganglia, whose axonal projections innervate the abdominal neurohaemal organs, where these neurohormones are released into circulation. Lastly, pharmacological inhibition of nitric oxide synthase (NOS) and protein kinase G (PKG) signaling eliminated anti-diuretic activity of CAPA, highlighting the role of the second messenger cGMP and NOS/PKG in this anti-diuretic signaling pathway.
Highlights
Insect CAPA neuropeptides are homologs of mammalian neuromedin U and are known to influence ion and water balance by regulating the activity of the Malpighian ‘renal’ tubules (MTs)
We recently identified an endogenous anti-diuretic hormone in the disease-vector mosquito, Aedes aegypti, that strongly inhibits select diuretic factors including the mosquito natriuretic peptide[37], which is critical for the post-prandial sodium-rich diuresis that follows blood gorging by adult females[22]
The gene structure model revealed the cloned cDNA mapped to eleven exons spanning a genomic region of over 351 Kb, with the start codon positioned within the third exon and the translation termination codon located in the eleventh exon, which contains the predicted polyadenylation signal at nucleotide position 3405–3410 (Fig. S1B)
Summary
Insect CAPA neuropeptides are homologs of mammalian neuromedin U and are known to influence ion and water balance by regulating the activity of the Malpighian ‘renal’ tubules (MTs). Anti-diuretic activity of CAPA neuropeptides has been reported earlier in larval A. aegypti[36] as well as in other insects[31,38,39,40,41,42], with signaling involving cGMP as a second messenger[31,37,40,42,43]. In addition to their clear anti-diuretic roles, CAPA peptides have been linked to desiccation, where desiccation stress in Drosophila melanogaster leads to upregulation of capa mRNA, which is suggested to elevate CAPA levels in the CNS44. Our data provides further evidence that mosquito CAPA neuropeptides, together with their cognate receptor identified function in a neuroendocrine system halting the stimulatory activity of diuretic hormones that, if left unregulated, may compromise ion and water homeostasis in this important anthropophilic mosquito
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