Biology subjects

Paluzzi, J.-P.

Publications and source records attributed to Paluzzi, J.-P..

3 recordsLinked to original sources

bioRxiv2022

Octopamine and tyramine signaling in Aedes aegypti: characterization, distribution and potential role in the Dengue vector development and physiology

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 previously reported on their OA or TA receptors. Here, we identify and characterize the OA and TA receptors in A. aegypti. Bioinformatic tools have been 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 compared to the larval stages. 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 hypothesize 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 signaling in A. aegypti, the transcript expression profiles of key enzymes in their biosynthetic pathway, namely tyrosine decarboxylase (Tdc) and tyramine {beta}-hydroxylase (T{beta}h), 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. Author summaryAedes aegypti is the primary vector for dengue, chikungunya, and yellow fever - debilitating diseases that together are responsible for hundreds of millions of infections and thousands of deaths annually worldwide. Understanding the A. aegypti physiology may be critical for the development of new control strategies. In insects, the biogenic amines dopamine, serotonin, tyramine and octopamine play important roles in controlling various physiological processes. In A. aegypti, both serotonin and dopamine are implicated in blood feeding behavior and development. Conversely, the role of octopamine (OA) and tyramine (TA) in A. aegypti physiology is still poorly characterized. Both OA and TA exert their physiological actions by interacting with and activating different receptors, the tyramine (TAR) and the octopamine (OAR) receptors. Here, we show the characterization of the OA and TA receptors in A. aegypti. In the A. aegypti genome we identify a total of four OA receptors and three TA receptors, suggesting for each receptor a particular role in the development and physiology of this insect. This work contributes to better understanding the roles of OA, TA, and their receptors, in A. aegypti development and physiology. Furthermore, it may be crucial in identifying novel strategies for the mosquitoes control.

zoology↗

bioRxiv2019

Insight into mosquito GnRH-related neuropeptide receptor specificity revealed through analysis of naturally occurring and synthetic analogs of this neuropeptide family

Adipokinetic hormone (AKH), corzazonin (CRZ) and the AKH/CRZ-related peptide (ACP) are peptides considered homologous to the vertebrate gonadotropin-releasing hormone (GnRH). All three Aedes aegypti GnRH-related neuropeptide receptors have been characterized and functionally deorphanized, which individually exhibit high specificity for their native ligands, which prompted us to investigate the contribution of ligand structures in conferring receptor specificity. In the current study, we designed a series of analogs based on the native ACP sequence in A. aegypti and screened them against the ACP receptor using a heterologous system to identify critical residues required for receptor activation. Specifically, analogs lacking the carboxy-terminal amidation, replacing aromatic residues, as well as truncated analogs were either completely inactive or had very low activities even at high concentration. The next most critical residues were the polar threonine in position 3 and the blocked amino-terminal pyroglutamate, with activity of the latter partially recovered using an alternatively blocked analog. ACP analogs with alanine substitutions at position 2 (valine), 5 (serine), 6 (arginine) and 7 (aspartic acid) positions were less detrimental as were replacements of charged residues. Interestingly, replacing asparagine with an alanine at position 9, creating a C-terminal WAA-amide, resulted in a 5-fold more active analog which may be useful as a lead superagonist compound. Similarly, we utilized this high-throughput approach against an A. aegypti AKH receptor (AKHR-IA) testing a number of mostly naturally-occurring AKH analogs from other insects to determine how substitutions of specific amino acids in the AKH ligand influences receptor activation. AKH analogs having single substitutions compared to the endogenous A. aegypti AKH revealed position 7 (serine) was well tolerated whereas changes to position 6 (proline) had pronounced effects, with receptor activity compromised nearly ten-fold. Substitution of position 3 (threonine) or analogs with combinations of substitutions were quite detrimental with a significant decrease in AKHR-IA activation. Interestingly, analogs with an asparagine residue at position seven displayed improved receptor activation compared to the native mosquito AKH. Collectively, these results advance our understanding of how two GnRH-related systems in A. aegypti sharing the most recent evolutionary origin sustain independence of function and signalling despite their relatively high degree of ligand and receptor homology.

physiology↗

bioRxiv2019

Corazonin neuroendocrine pathway orchestrates stress-associated physiology in Drosophila

Environmental factors challenge the physiological homeostasis in animals, thereby evoking stress responses. Various mechanisms have evolved to counter stress at the organism level, including regulation by neuropeptides. In recent years, much progress has been made on the mechanisms and neuropeptides that regulate responses to metabolic/nutritional stress, as well as those involved in countering osmotic and ionic stresses. Here, we identified a peptidergic pathway that links these types of regulatory functions. We uncover the neuropeptide Corazonin (Crz), previously implicated in responses to metabolic stress, as a neuroendocrine factor that inhibits the release of a diuretic hormone, CAPA, and thereby modulates the tolerance to osmotic and ionic stress. Both knockdown of Crz and acute injections of Crz peptide impact desiccation tolerance and recovery from chill-coma. Mapping of the Crz receptor (CrzR) expression identified three pairs of Capa-expressing neurons (Va neurons) in the ventral nerve cord that mediate these effects of Crz. We show that Crz acts to restore water/ion homeostasis by inhibiting release of CAPA neuropeptides via inhibition of cAMP production in Va neurons. Knockdown of CrzR in Va neurons affects CAPA signaling, and consequently increases tolerance for desiccation, ionic stress and starvation, but delays chill-coma recovery. Optogenetic activation of Va neurons stimulates excretion and simultaneous activation of Crz and CAPA-expressing neurons reduces this response, supporting the inhibitory action of Crz. Thus, Crz inhibits Va neurons to maintain osmotic and ionic homeostasis, which in turn affects stress tolerance. Earlier work demonstrated that systemic Crz signaling restores nutrient levels by promoting food search and feeding. Here we additionally propose that Crz signaling also ensures osmotic homeostasis by inhibiting release of CAPA neuropeptides and suppressing diuresis. Thus, Crz ameliorates stress-associated physiology through systemic modulation of both peptidergic neurosecretory cells and the fat body in Drosophila. Author summaryInsects are among the largest groups of animals and have adapted to inhabit almost all environments on Earth. Their success in surviving extreme conditions stems largely from their ability to withstand environmental stress, such as desiccation and cold. However, the neural mechanisms that are responsible for coordinating responses to counter these stresses are largely unknown. To address this, we delineate a neuroendocrine axis utilizing the neuropeptides Corazonin (Crz) and CAPA, that coordinate responses to metabolic and osmotic stress. We show that Crz inhibits the release of a diuretic peptide, CAPA from a set of neurosecretory cells. CAPA in turn influences osmotic and ionic balance via actions on the Malpighian tubules (the insect analogs of the kidney) and the intestine. Taken together with earlier work, our data suggest that Crz acts to restore metabolic homeostasis at starvation and osmotic homeostasis during desiccation by inhibiting release of the diuretic hormone CAPA. Hence, this work provides a mechanistic understanding of the neuroendocrine mitigation of metabolic and osmotic stress by two peptide systems.

neuroscience↗