Dataset Information

Pharmacological Characterization of the Stick Insect Carausius morosus Allatostatin-C Receptor with Its Endogenous Agonist.

ABSTRACT: G protein-coupled receptors (GPCRs) play a pivotal role in regulating key physiological events in all animal species. Recent advances in collective analysis of genes and proteins revealed numerous potential neuropeptides and GPCRs from insect species, allowing for the characterization of peptide-receptor pairs. In this work, we used fluorescence resonance energy transfer (FRET)-based genetically encoded biosensors in intact mammalian cells to study the pharmacological features of the cognate GPCR of the type-C allatostatin (AST-C) peptide from the stick insect, Carausius morosus. Analysis of multiple downstream pathways revealed that AST-C can activate the human Gi₂ protein, and not Gs or Gq, through AST-C receptor (AlstRC). Activated AlstRC recruits ?-arrestin2 independent of the Gi protein but stimulates ERK phosphorylation in a Gi protein-dependent manner. Identification of G?i-, arrestin-, and GRK-like transcripts from C. morosus revealed high evolutionary conservation at the G protein level, while ?-arrestins and GRKs displayed less conservation. In conclusion, our study provides experimental and homology-based evidence on the functionality of vertebrate G proteins and downstream signaling biosensors to characterize early signaling steps of an insect GPCR. These results may serve as a scaffold for developing assays to characterize pharmacological and structural aspects of other insect GPCRs and can be used in deorphanization and pesticide studies.

SUBMITTER: Isbilir A

PROVIDER: S-EPMC7758886 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Pharmacological Characterization of the Stick Insect <i>Carausius morosus</i> Allatostatin-C Receptor with Its Endogenous Agonist.

Işbilir Ali A Duan Sahbaz Burcin B Tuncgenc Gunes G Bünemann Moritz M Lohse Martin J MJ Birgül-Iyison Necla N

ACS omega 20201208 50

G protein-coupled receptors (GPCRs) play a pivotal role in regulating key physiological events in all animal species. Recent advances in collective analysis of genes and proteins revealed numerous potential neuropeptides and GPCRs from insect species, allowing for the characterization of peptide-receptor pairs. In this work, we used fluorescence resonance energy transfer (FRET)-based genetically encoded biosensors in intact mammalian cells to study the pharmacological features of the cognate GPC ...[more]

PMID: 33376856

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Project description:The corpora cardiaca of the Indian stick insect, Carausius morosus, synthesize two decapeptide neuropeptides of the adipokinetic hormone (AKH) family, both of which can increase the trehalose levels in the hemolymph when the stick insect is ligated between the head and the thorax. Here, we use two biological assays to assess the potencies of 19 AKH analogs in ligated C. morosus: the carbohydrate-mobilizing assay measures the change in the levels of circulating carbohydrates following injection of a substance, while the semi-exposed heart assay measures a change in heart beat rate after the peptide is applied onto the heart. With the endogenous AKH (Carmo-HrTH-II) as lead peptide, we report here on seven naturally-occurring AKH peptides (bioanalogs) selected for testing because of a single or double amino acid replacement, or for being octapeptides. Single amino acid substitutions by an alanine residue at all positions of Carmo-HrTH-II, as well as analogs modified at the termini were also investigated to give a comprehensive view of ligand-receptor interaction at the physiological level in a hemimetabolous insect that practices thanatosis (feigning death). Only small changes are elicited in the bioassays, but the results from the two tests are comparable bar one or two anomalies. Results show that analogs modified at the termini have no or reduced activity. Regarding structural requirements of a ligand, the C. morosus AKH receptor appears to be strict: octapeptides are not preferred and many of the decapeptide analogs failed to reach 50% activity relative to Carmo-HrTH-II. The data implies that the AKH receptor in C. morosus mostly does not tolerate shorter peptides and single amino acid replacements in most places of the native AKH peptide. This information is important if environmentally friendly insect-specific pesticides are made based on an insect AKH as lead peptide: stick insects that are normally not viewed as pest insects may not be easily targeted by cross-reactive AKH mimetics directed at harmful insects, due to the very specific amino acid requirements to activate the C. morosus AKH receptor.

Dataset Information

Pharmacological Characterization of the Stick Insect Carausius morosus Allatostatin-C Receptor with Its Endogenous Agonist.

Publications

Pharmacological Characterization of the Stick Insect <i>Carausius morosus</i> Allatostatin-C Receptor with Its Endogenous Agonist.

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